Details of the Researcher

PHOTO

Eikan Mishima
Section
Graduate School of Medicine
Job title
Professor
Degree
e-Rad No.
00706939
Profile

細胞死の一種であるフェロトーシス（Ferroptosis）のバイオロジーと病気への関わりの解明が現在のメイン研究テーマです。

フェロトーシスは鉄介在性脂質過酸化依存性の細胞死で、さまざまな病気との関連が近年知られ、創薬標的としても世界的に注目されています。我々の分野ではフェロトーシスを標的にしたがんや臓器障害、変性疾患の病態の解明および治療薬の開発を目指しています。

また、生物の進化学的な観点からなぜフェロトーシスによる細胞死が生体には存在していて、どのように制御されているかに興味を持っています。さらに今後本分野では、フェロトーシスにとどまらず、レドックス生物学に関連する多様な現象や、未だ十分に解明されていない新規細胞死様式の探索にも取り組み、生命科学の未踏領域の開拓を目指してまいります。また、臨床医としての経験を持つことを生かして、基礎研究と臨床研究の融合を通じて、環境と健康の関係性をより深く理解し、その成果を社会へ還元すること目標にしています。

分野HP：https://www.env.med.tohoku.ac.jp/

分野 X アカウント：https://x.com/EMishima_lab

Research History 15

  • 2026/04 - Present
    Tohoku University Graduate School of Medicine　Environmental Medicine and Molecular Toxicology　Professor

  • 2023/03 - 2026/03
    ヘルムホルツセンター・ミュンヘン　上級研究員、グループリーダー

  • 2020/10 - 2026/03
    Tohoku University of Medicine　Division of Nephrology, Rheumatology and Endocrinology　Researcher

  • 2020/10 - 2023/02
    Helmholtz Zentrum München　Institute of Metabolism and Cell Death　Guest scientist

  • 2019/04 - 2020/09
    Tohoku University Graduate School of Medicine　University Hospital Nephrology, Endocrinology and Vascular Medicine　Associate professor / lecturer

  • 2016/02 - 2019/03
    Tohoku University Graduate School of Medicine　Division of Nephrology, Endocrinology and Vascular Medicine　Assistant Professor

  • 2013/04 - 2016/01
    Tohoku University　Tohoku Medical Megabank Organization　Assistant Professor

  • 2015/06 - 2015/09
    公立志津川病院 南三陸診療所 内科医長

  • 2014/08 - 2014/09
    石巻赤十字病院 内科 医師

  • 2014/06 - 2014/07
    公立志津川病院 南三陸診療所 内科医長

  • 2013/06 - 2013/09
    公立志津川病院 南三陸診療所 内科医長

  • 2009/04 - 2013/03
    Tohoku University School of medicine　Graduate student

  • 2008/04 - 2009/03
    The University of Tokyo　Division of Nephrology and Endocrinology　Senior resident

  • 2006/04 - 2008/03
    Osaki Citizen Hospital　Resident

  • 2000/04 - 2006/03
    Tohoku University School of medicine

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Committee Memberships 10

  • Editorial borad member, BMC Nephrology

    2020 - Present

  • 日本高血圧学会 国際交流委員会

    2020 - Present

  • 日本腎臓学会 広報委員会

    2019 - Present

  • 日本高血圧学会 U-45委員会

    2023 - 2024

  • 日本腎臓学会　JSN Next Frontiers 2028委員会

    2018 - 2024

  • 国際高血圧学会 ISH2022 Kyoto, Support member

    2021 - 2022

  • 日本腎臓学会 専門医試験症例評価委員

    2021 - 2022

  • 日本高血圧学会　若手活性化委員会

    2017 - 2021

  • 日本高血圧学会　高血圧ガイドライン2019作成委員会

    2017 - 2019

  • ISN Frontier Meeting (Tokyo)　Local organizing committee member

    2017 - 2018

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Professional Memberships 6

  • 分子生物学会

  • 日本心血管内分泌代謝学会

  • THE JAPANESE SOCIETY OF INTERNAL MEDICINE

  • The Japan Endocrine Society

  • The Japanese Society of Hypertension

  • JAPANESE SOCIETY OF NEPHROLOGY

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Research Interests 8

  • Redox Biology

  • Lipie peroxidation

  • Oxidative stress

  • Ferroptosis

  • Cell death

  • Metabolome

  • Hypertension

  • Nephrology

Research Areas 3

  • Life sciences / Molecular biology /

  • Life sciences / Metabolism and endocrinology /

  • Life sciences / Nephrology /

Awards 34

  1. 高峰譲吉研究奨励賞

    2024　心血管内分泌学会

  2. 三島海雲学術賞

    2023

  3. 奨励賞

    2023　日本ビタミン学会

  4. 安藤百福賞 発明発見奨励賞

    2023

  5. Oshima Award

    2023　JSN

  6. Helmholtz Munich Best Paper Award 2022

    2022

  7. 第9回臨床高血圧フォーラム 優秀演題賞

    2021

  8. 上原記念生命科学財団 海外留学助成リサーチフェローシップ

    2020

  9. 東北大学 今野海外留学奨励賞

    2020

  10. 第18回インテリジェントコスモス奨励賞

    2019

  11. 第116回日本内科学会総会 医学生研修医の「日本内科学会ことはじめ2019名古屋」指導教官賞

    2019

  12. 第8回臨床高血圧フォーラム 症例報告優秀賞

    2019

  13. 第10回分子腎臓フォーラム 優秀演題賞

    2019

  14. 第31回フリーラジカル研究会 最優秀奨励賞

    2019

  15. Japan Kidney Council 2019 優秀賞

    2019

  16. Best English Presentation Award

    2018　第61回日本腎臓学会学術総会

  17. 優秀症例報告賞

    2018　第7回臨床高血圧フォーラム

  18. 優秀論文賞

    2018　第21回 日本腎臓学会

  19. 奨学賞（銀賞）

    2018　平成29年度東北大学医学部

  20. Investigator Award

    2017　The 6th Chronic Kidney Disease Frontier Meeting

  21. 最優秀演題賞

    2017　第1回 日本Uremic Toxin研究会学術集会

  22. 特別奨励賞

    2016　第7回 腎不全研究会

  23. 優秀演題賞

    2016　第59回 日本腎臓学会学術総会

  24. 指導教官賞

    2016　第113回 日本内科学会総会 医学生・研修医の「日本内科学会ことはじめ2016東京」

  25. 優秀演題賞

    2015　第58回 日本腎臓学会学術総会

  26. 指導教官賞

    2015　第112回 日本内科学会総会 医学生・研修医の「日本内科学会ことはじめ2015京都」

  27. Investigator Award

    2014　The 4th Chronic Kidney Disease Frontier Meeting

  28. 優秀演題賞

    2014　第57回 日本腎臓学会学術総会

  29. Young Investigator’s Question Award

    2013　第6回 リトリート大学院生研究発表会

  30. 特別奨励賞受賞

    2012　第3回腎不全研究会

  31. Young Investigator’s Question Award

    2012　第5回 リトリート大学院生研究発表会

  32. 優秀演題賞

    2011　第54回 日本腎臓学会学術総会

  33. Young Investigator’s Question Award

    2011　第4回 リトリート大学院生研究発表会

  34. 優秀発表賞

    2011　第5回 トランスポーター研究会年会

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Papers 162

  1. Electrophilic monocarbonyl curcumin derivatives reveal differential vulnerabilities in the selenium metabolic network. International-journal

    Wang Yinuo, Takashi Toyama, Hiroyuki Yamakoshi, Hiroki Taguchi, Hayato Takashima, Ryo Watanabe, Yuichiro Mita, Junya Ito, Eikan Mishima, Yasutoshi Akiyama, Hiroyuki Shibata, Noriko Noguchi, Toshinari Takamura, Marcus Conrad, Yoshihisa Tomikoka, Yoshiharu Iwabuchi, Yoshiro Saito

    Free radical biology & medicine　253　487-499　2026/06/02

    DOI： 10.1016/j.freeradbiomed.2026.06.004 　

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    Selenium is an essential trace element whose biological functions are exerted through selenoproteins, synthesized by a highly coordinated and redox-regulated network. How this network responds to electrophilic stimulus, however, remains incompletely understood. Here, we employed a focused library of monocarbonyl curcumin derivatives as electrophilic chemical tools to interrogate the selenium metabolic network. Screening based on intracellular selenoprotein P abundance identified GO-Y015 as a potent and low-toxicity compound capable of strongly changing expression of selenoprotein P and glutathione peroxidase. In cultured hepatocytes, GO-Y015 suppressed selenoprotein expression by inhibiting de novo selenoprotein synthesis, rather than promoting lysosomal degradation. Biochemical analyses revealed that GO-Y015 covalently modified multiple selenium-handling enzymes, including PRDX6, SCLY, and SEPHS2, and impaired selenium incorporation into Sec-tRNA, indicating broader alternation of selenium metabolism. Short-term administration of GO-Y015 in mice resulted in a selective reduction of circulating selenoprotein P, with limited effects on other selenoproteins and no overt hepatotoxicity. Under these conditions, no body-weight loss and hepatotoxicity was observed, supporting the interpretation that the observed molecular effects reflect acute metabolic alteration. Together, these findings establish electrophilic monocarbonyl curcumin derivatives as chemical tools that reveal differential vulnerabilities within the selenium metabolic network, with selenoprotein P serving as a particularly sensitive indicator of selenium metabolic modulation.

  2. Fat bolsters tumours against ferroptosis

    Eikan Mishima, Marcus Conrad

    Nature Cell Biology　2026/04

    DOI： 10.1038/s41556-026-01904-0 　

  3. Tocotrienols exhibit superior ferroptosis inhibition over tocopherols

    Hao Yang, Junya Ito, Taiki Maejima, Shinnosuke Kimura, Hikaru Ino, Yusuke Hirata, Atsushi Matsuzawa, Sho Kobayashi, Eikan Mishima, Kiyotaka Nakagawa

    Scientific Reports　2026/01/07

    Publisher: Springer Science and Business Media LLC

    DOI： 10.1038/s41598-025-34673-1 　

    eISSN： 2045-2322

  4. Arsenite sensitizes to ferroptosis by disrupting selenium metabolism and reducing GPx4 expression

    Hayato Takashima, Reiko Makino, Hiroki Taguchi, Junya Ito, Eikan Mishima, Yoshika Takenaka, Yasutoshi Akiyama, Daigo Sumi, Marcus Conrad, Yoshihisa Tomikoka, Takashi Toyama, Yoshiro Saito

    Toxicology　154409-154409　2026/01

    Publisher: Elsevier BV

    DOI： 10.1016/j.tox.2026.154409 　

    ISSN： 0300-483X

  5. A fin-loop-like structure in GPX4 underlies neuroprotection from ferroptosis. International-journal

    Svenja M Lorenz, Adam Wahida, Mark J Bostock, Tobias Seibt, André Santos Dias Mourão, Anastasia Levkina, Dietrich Trümbach, Mohamed Soudy, David Emler, Nicola Rothammer, Marcel S Woo, Jana K Sonner, Mariia Novikova, Bernhard Henkelmann, Maceler Aldrovandi, Daniel F Kaemena, Eikan Mishima, Perrine Vermonden, Zhi Zong, Deng Cheng, Toshitaka Nakamura, Junya Ito, Sebastian Doll, Bettina Proneth, Erika Bürkle, Francesca Rizzollo, Abril Escamilla Ayala, Valeria Napolitano, Marta Kolonko-Adamska, Stefan Gaussmann, Juliane Merl-Pham, Stefanie Hauck, Anna Pertek, Tanja Orschmann, Emily van San, Tom Vanden Berghe, Daniela Hass, Adriano Maida, Joris M Frenz, Lohans Pedrera, Amalia Dolga, Markus Kraiger, Martin Hrabé de Angelis, Helmut Fuchs, Gregor Ebert, Jerica Lenberg, Jennifer Friedman, Carolin Scale, Patrizia Agostinis, Annemarie Zimprich, Daniela Vogt-Weisenhorn, Lillian Garrett, Sabine M Hölter, Wolfgang Wurst, Enrico Glaab, Jan Lewerenz, Bastian Popper, Christian Sieben, Petra Steinacker, Hans Zischka, Ana J Garcia-Saez, Anna Tietze, Sanath Kumar Ramesh, Scott Ayton, Michelle Vincendeau, Manuel A Friese, Kristen Wigby, Michael Sattler, Matthias Mann, Irina Ingold, Ashok Kumar Jayavelu, Grzegorz M Popowicz, Marcus Conrad

    Cell　2025/12/04

    DOI： 10.1016/j.cell.2025.11.014 　

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    Ferroptosis, driven by uncontrolled peroxidation of membrane phospholipids, is distinct from other cell death modalities because it lacks an initiating signal and is surveilled by endogenous antioxidant defenses. Glutathione peroxidase 4 (GPX4) is the guardian of ferroptosis, although its membrane-protective function remains poorly understood. Here, structural and functional analyses of a missense mutation in GPX4 (p.R152H), which causes early-onset neurodegeneration, revealed that this variant disrupts membrane anchoring without considerably impairing its catalytic activity. Spatiotemporal Gpx4 deletion or neuron-specific GPX4R152H expression in mice induced degeneration of cortical and cerebellar neurons, accompanied by progressive neuroinflammation. Patient induced pluripotent stem cell (iPSC)-derived cortical neurons and forebrain organoids displayed increased ferroptotic vulnerability, mirroring key pathological features, and were sensitive to ferroptosis inhibition. Neuroproteomics revealed Alzheimer's-like signatures in affected brains. These findings highlight the necessity of proper GPX4 membrane anchoring, establish ferroptosis as a key driver of neurodegeneration, and provide the rationale for targeting ferroptosis as a therapeutic strategy in neurodegenerative disease.

  6. Lubiprostone in Chronic Kidney Disease: Insights into Mitochondrial Function and Polyamines from a Randomized Phase 2 Clinical Trial

    Yuji Naito, Koichi Kikuchi, Yoshihisa Tomioka, Takuji Yamada, Kei Fukami, Yusuke Suzuki, Shun Itai, Eikan Mishima, Shinji Fukuda, Masaaki Nakayama, Satoru Sanada, Yoshifumi Ubara, Tsuneo Konta, Junichiro James Kazama, Yoshiyasu Tongu, Chiharu Kawabe, Takashi Yokoo, Katsuhiko Asanuma, Yasu Akiyama, Atsushi Komatsuda, Yoshiaki Ogata, Hidetaka Tokuno, Sayaka Mizutani, Shun Watanabe, Marina Urasato, Mitsuharu Matsumoto, Chitose Suzuki, Tomoko Kasahara, Tetsuhiro Tanaka, Tomoyoshi Soga, Takehiro Suzuki, Hitomi Kashiwagi, LUBI-CKD TRIAL Investigators, Kensei Taguchi, Takafumi Toyohara, Ryota Kujirai, Takaaki ABE, Yotaro Matsumoto, Takeya Sato

    Science Advances　2025/08/29

    DOI： 10.1126/sciadv.adw3934 　

  7. Recommendations for robust and reproducible research on ferroptosis

    Eikan Mishima, Toshitaka Nakamura, Sebastian Doll, Bettina Proneth, Maria Fedorova, Derek A. Pratt, José Pedro Friedmann Angeli, Scott J. Dixon, Adam Wahida, Marcus Conrad

    Nature Reviews Molecular Cell Biology　2025/08

    DOI： 10.1038/s41580-025-00843-2 　

  8. Lactoferrin attenuates renal fibrosis and uremic sarcopenia in a mouse model of adenine-induced chronic kidney disease

    Yukina Iwamoto, Seiko Yamakoshi, Akiyo Sekimoto, Koji Hosomi, Takashi Toyama, Yoshiro Saito, Jun Kunisawa, Nobuyuki Takahashi, Eikan Mishima, Emiko Sato

    The Journal of Nutritional Biochemistry　110039-110039　2025/07

    Publisher: Elsevier BV

    DOI： 10.1016/j.jnutbio.2025.110039 　

    ISSN： 0955-2863

  9. MALT1 inhibitor MI-2 induces ferroptosis by direct targeting of GPX4. International-journal

    Eikan Mishima, Thomas J O'Neill, Kai P Hoefig, Deng Chen, Gesine Behrens, Bernhard Henkelmann, Junya Ito, Kiyotaka Nakagawa, Vigo Heissmeyer, Marcus Conrad, Daniel Krappmann

    Proceedings of the National Academy of Sciences of the United States of America　122　(20)　e2507997122　2025/05/20

    DOI： 10.1073/pnas.2507997122 　

  10. ALDH7A1 protects against ferroptosis by generating membrane NADH and regulating FSP1. International-journal

    Jia-Shu Yang, Andrew J Morris, Koki Kamizaki, Jianzhong Chen, Jillian Stark, William M Oldham, Toshitaka Nakamura, Eikan Mishima, Joseph Loscalzo, Yasuhiro Minami, Marcus Conrad, Whitney S Henry, Victor W Hsu

    Cell　188　(10)　2569-2585　2025/05/15

    DOI： 10.1016/j.cell.2025.03.019 　

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    Ferroptosis is a form of cell death due to iron-induced lipid peroxidation. Ferroptosis suppressor protein 1 (FSP1) protects against this death by generating antioxidants, which requires nicotinamide adenine dinucleotide, reduced form (NADH) as a cofactor. We initially uncover that NADH exists at significant levels on cellular membranes and then find that this form of NADH is generated by aldehyde dehydrogenase 7A1 (ALDH7A1) to support FSP1 activity. ALDH7A1 activity also acts directly to decrease lipid peroxidation by consuming reactive aldehydes. Furthermore, ALDH7A1 promotes the membrane recruitment of FSP1, which is instigated by ferroptotic stress activating AMP-activated protein kinase (AMPK) to promote the membrane localization of ALDH7A1 that stabilizes FSP1 on membranes. These findings advance a fundamental understanding of NADH by revealing a previously unappreciated pool on cellular membranes, with the elucidation of its function providing a major understanding of how FSP1 acts and how an aldehyde dehydrogenase protects against ferroptosis.

  11. N-acetyl-l-cysteine averts ferroptosis by fostering glutathione peroxidase 4. International-journal

    Jiashuo Zheng, Weijia Zhang, Junya Ito, Bernhard Henkelmann, Chenxi Xu, Eikan Mishima, Marcus Conrad

    Cell chemical biology　32　(5)　767-775　2025/05/15

    DOI： 10.1016/j.chembiol.2025.04.002 　

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    N-acetyl-l-cysteine (NAC) is a medication and a widely used antioxidant in cell death research. Despite its somewhat obscure mechanism of action, its role in inhibiting ferroptosis is gaining increasing recognition. In this study, we demonstrate that NAC treatment rapidly replenishes the intracellular cysteine pool, reinforcing its function as a prodrug for cysteine. Interestingly, its enantiomer, N-acetyl-d-cysteine (d-NAC), which cannot be converted into cysteine, also exhibits a strong anti-ferroptotic effect. We further clarify that NAC, d-NAC, and cysteine all act as direct reducing substrates for GPX4, counteracting lipid peroxidation. Consequently, only GPX4-rather than system xc-, glutathione biosynthesis, or ferroptosis suppressor protein 1-is necessary for NAC and d-NAC to prevent ferroptosis. Additionally, we identify a broad range of reducing substrates for GPX4 in vitro, including β-mercaptoethanol. These findings provide new insights into the mechanisms underlying the protective effects of NAC and other potential GPX4-reducing substrates against ferroptosis.

  12. Supersulfides contribute to joint homeostasis and bone regeneration. International-journal

    Miki Maemura, Masanobu Morita, Seiryo Ogata, Yoichi Miyamoto, Tomoaki Ida, Kazuhiro Shibusaka, Soichiro Negishi, Masahiro Hosonuma, Taku Saito, Jun Yoshitake, Tsuyoshi Takata, Tetsuro Matsunaga, Eikan Mishima, Uladzimir Barayeu, Takaaki Akaike, Fumiko Yano

    Redox biology　81　103545-103545　2025/04

    DOI： 10.1016/j.redox.2025.103545 　

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    The physiological functions of supersulfides, inorganic and organic sulfides with sulfur catenation, have been extensively studied. Their synthesis is mainly mediated by mitochondrial cysteinyl-tRNA synthetase (CARS2) that functions as a principal cysteine persulfide synthase. This study aimed to investigate the role of supersulfides in joint homeostasis and bone regeneration. Using Cars2AINK/+ mutant mice, in which the KIIK motif of CARS2 essential for supersulfide production was replaced with AINK, we evaluated the role of supersulfides in fracture healing and cartilage homeostasis during osteoarthritis (OA). Tibial fracture surgery was performed on the wild-type (Cars2+/+) and Cars2AINK/+ mice littermates. Bulk RNA-seq analysis for the osteochondral regeneration in the fracture model showed increased inflammatory markers and reduced osteogenic factors, indicative of impaired bone regeneration, in Cars2AINK/+ mice. Destabilization of the medial meniscus (DMM) surgery was performed to produce the mouse OA model. Histological analyses with Osteoarthritis Research Society International and synovitis scores revealed accelerated OA progression in Cars2AINK/+ mice compared with that in Cars2+/+ mice. To assess the effects of supersulfides on OA progression, glutathione trisulfide (GSSSG) or saline was periodically injected into the mouse knee joints after the DMM surgery. Thus, supersulfides derived from CARS2 and GSSSG exogenously administered significantly inhibited inflammation and lipid peroxidation of the joint cartilage, possibly through suppression of ferroptosis, during OA development. This study represents a significant advancement in understanding anti-inflammatory and anti-oxidant functions of supersulfides in skeletal tissues and may have a clinical relevance for the bone healing and OA therapeutics.

  13. PRDX6 dictates ferroptosis sensitivity by directing cellular selenium utilization

    Junya Ito, Toshitaka Nakamura, Takashi Toyama, Deng Chen, Carsten Berndt, Gereon Poschmann, André Santos Dias Mourão, Sebastian Doll, Mirai Suzuki, Weijia Zhang, Jiashuo Zheng, Dietrich Trümbach, Naoya Yamada, Koya Ono, Masana Yazaki, Yasutaka Kawai, Mieko Arisawa, Yusuke Ohsaki, Hitoshi Shirakawa, Adam Wahida, Bettina Proneth, Yoshiro Saito, Kiyotaka Nakagawa, Eikan Mishima, Marcus Conrad

    Molecular Cell　2024/11

    Publisher: Elsevier BV

    DOI： 10.1016/j.molcel.2024.10.028 　

    ISSN： 1097-2765

  14. Ferroptotic vulnerability of post-meiotic germ cells skews sex chromosome ratios in aged testis

    Jasper Germeraad, Takako Kikkawa, Junya Ito, Leon S.Y Giesselink, Wilfred T.V Germeraad, Bernhard Henkelmann, Maceler Aldrovandi, Kenshiro Hara, Kentaro Tanemura, Kiyotaka Nakagawa, Eikan Mishima, Marcus Conrad, Noriko Osumi

    2024/10/24

    Publisher: openRxiv

    DOI： 10.1101/2024.10.21.619554 　

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    Germ cell depletion in the aged testes has traditionally been attributed to removal by apoptosis. This study aimed to determine whether ferroptosis, an alternative form of cell death driven by iron dependent lipid peroxidation, also contributes to germ cell loss in the lipid rich environment of the testis. Here, we demonstrate that pre-meiotic cells are eliminated via apoptosis, whereas post-meiotic round spermatids (RSs) are mainly removed through ferroptosis. Surprisingly, we detected a greater abundance of Y chromosome bearing RSs (Y RSs) than X-carrying RSs (X RSs) in the aged testis, implying that X RSs might be more prone to ferroptosis. Young mice fed a vitamin E (VE) deficient diet recapitulated age-related phenotypes, while VE supplementation prevented ferroptosis and promoted the survival of X RSs in aged mice. Overall, this study reveals that aging causes ferroptosis in RSs, specifically impacting X RSs, which can be prevented by VE supplementation, effectively reversing age induced deterioration and contributing to healthy testicular aging.

  15. Impacts of low birthweight on kidney development and intergenerational growth of the offspring International-journal

    Akiyo Sekimoto, Yoko Takaso, Haruka Saruyama, Masataka Ookawa, Mari Yamamoto, Takafumi Toyohara, Daisuke Saigusa, Tomoko Fukuuchi, Mayu Otsuka, Yui Fushiki, Seiko Yamakoshi, Kayo Tanaka, Tomoaki Ikeda, Tetsuhiro Tanaka, Nobuyuki Takahashi, Eikan Mishima, Emiko Sato

    iScience　27　(11)　111159-111159　2024/10

    Publisher: Elsevier BV

    DOI： 10.1016/j.isci.2024.111159 　

    ISSN： 2589-0042

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    Low birthweight (LBW) increases the risk of adult-onset diseases, including kidney diseases, with intergenerational consequences; however, the underlying mechanisms and effective interventions are unclear. To examine the cross-generational effects of LBW, we established an LBW mouse model through reduced uterine perfusion pressure (RUPP) and investigated the therapeutic potential of tadalafil, a phosphodiesterase 5 inhibitor, on LBW-associated consequences. RUPP-pups (R1) had lower fetal and birth weights, delayed renal development, and fewer glomeruli than Sham-pups. In adulthood, R1 mice exhibited persistently fewer glomeruli and elevated blood pressure, while Tadalafil-R1 mice showed reduced hypertension in both sexes and improved renal pathological changes in males. Additionally, pregnant R1 mice displayed inadequate gestational liver hypertrophy, impaired hepatic purine metabolism, and diminished placental angiogenesis, resulting in fetal growth restriction in the subsequent generation. These findings underscore the lasting impact of LBW on adult health and future generations and suggest tadalafil's potential to mitigate LBW-associated risks.

  16. Ferroptosis in health and disease. International-journal

    Carsten Berndt, Hamed Alborzinia, Vera Skafar Amen, Scott Ayton, Uladzimir Barayeu, Alexander Bartelt, Hülya Bayir, Christina M Bebber, Kivanc Birsoy, Jan P Böttcher, Simone Brabletz, Thomas Brabletz, Ashley R Brown, Bernhard Brüne, Giorgia Bulli, Alix Bruneau, Quan Chen, Gina M DeNicola, Tobias P Dick, Ayelén Distéfano, Scott J Dixon, Jan B Engler, Julia Esser-von Bieren, Maria Fedorova, José Pedro Friedmann Angeli, Manuel A Friese, Dominic C Fuhrmann, Ana J García-Sáez, Karolina Garbowicz, Magdalena Götz, Wei Gu, Linda Hammerich, Behrouz Hassannia, Xuejun Jiang, Aicha Jeridi, Yun Pyo Kang, Valerian E Kagan, David B Konrad, Stefan Kotschi, Peng Lei, Marlène Le Tertre, Sima Lev, Deguang Liang, Andreas Linkermann, Carolin Lohr, Svenja Lorenz, Tom Luedde, Axel Methner, Bernhard Michalke, Anna V Milton, Junxia Min, Eikan Mishima, Sebastian Müller, Hozumi Motohashi, Martina U Muckenthaler, Shohei Murakami, James A Olzmann, Gabriela Pagnussat, Zijan Pan, Thales Papagiannakopoulos, Lohans Pedrera Puentes, Derek A Pratt, Bettina Proneth, Lukas Ramsauer, Raphael Rodriguez, Yoshiro Saito, Felix Schmidt, Carina Schmitt, Almut Schulze, Annemarie Schwab, Anna Schwantes, Mariluz Soula, Benedikt Spitzlberger, Brent R Stockwell, Leonie Thewes, Oliver Thorn-Seshold, Shinya Toyokuni, Wulf Tonnus, Andreas Trumpp, Peter Vandenabeele, Tom Vanden Berghe, Vivek Venkataramani, Felix C E Vogel, Silvia von Karstedt, Fudi Wang, Frank Westermann, Chantal Wientjens, Christoph Wilhelm, Michele Wölk, Katherine Wu, Xin Yang, Fan Yu, Yilong Zou, Marcus Conrad

    Redox biology　75　103211-103211　2024/09

    DOI： 10.1016/j.redox.2024.103211 　

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    Ferroptosis is a pervasive non-apoptotic form of cell death highly relevant in various degenerative diseases and malignancies. The hallmark of ferroptosis is uncontrolled and overwhelming peroxidation of polyunsaturated fatty acids contained in membrane phospholipids, which eventually leads to rupture of the plasma membrane. Ferroptosis is unique in that it is essentially a spontaneous, uncatalyzed chemical process based on perturbed iron and redox homeostasis contributing to the cell death process, but that it is nonetheless modulated by many metabolic nodes that impinge on the cells' susceptibility to ferroptosis. Among the various nodes affecting ferroptosis sensitivity, several have emerged as promising candidates for pharmacological intervention, rendering ferroptosis-related proteins attractive targets for the treatment of numerous currently incurable diseases. Herein, the current members of a Germany-wide research consortium focusing on ferroptosis research, as well as key external experts in ferroptosis who have made seminal contributions to this rapidly growing and exciting field of research, have gathered to provide a comprehensive, state-of-the-art review on ferroptosis. Specific topics include: basic mechanisms, in vivo relevance, specialized methodologies, chemical and pharmacological tools, and the potential contribution of ferroptosis to disease etiopathology and progression. We hope that this article will not only provide established scientists and newcomers to the field with an overview of the multiple facets of ferroptosis, but also encourage additional efforts to characterize further molecular pathways modulating ferroptosis, with the ultimate goal to develop novel pharmacotherapies to tackle the various diseases associated with - or caused by - ferroptosis.

  17. Targeting ferroptosis for treating kidney disease

    Eikan Mishima

    Clinical and Experimental Nephrology　2024/09

    DOI： 10.1007/s10157-024-02491-w 　

  18. 慢性腎臓病の早期診断法確立を目指した硫黄代謝物に基づく呼気オミックス

    逸見 佳宣, 緒方 星陵, 井田 智章, 三枝 大輔, 三島 英換, 高橋 信行, 魏 范研, 赤池 孝章, 佐藤 恵美子

    日本腎臓学会誌　66　(4)　632-632　2024/06

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  19. 慢性腎臓病の早期診断法確立を目指した硫黄代謝物に基づく呼気オミックス

    逸見 佳宣, 緒方 星陵, 井田 智章, 三枝 大輔, 三島 英換, 高橋 信行, 魏 范研, 赤池 孝章, 佐藤 恵美子

    日本腎臓学会誌　66　(4)　632-632　2024/06

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  20. Activation of lysosomal iron triggers ferroptosis in cancer International-journal

    Raphaël Rodriguez, Tatiana Cañeque, Leeroy Baron, Sebastian Müller, Alanis Carmona, Ludovic Colombeau, Antoine Versini, Marie Sabatier, Julio Sampaio, Eikan Mishima, Armel Picard-Bernes, Stéphanie Solier, Jiashuo Zheng, Bettina Proneth, Leishemba Thoidingjam, Christine Gaillet, Laurence Grimaud, Cameron Fraser, Krystina Szylo, Caroline Bonnet, Emmanuelle Charafe, Christophe Ginestier, Patricia Santofimia, Nelson Dusetti, Juan Iovanna, Antonio Sa Cunha, Gabriella Pittau, Pascal Hammel, Dimitri Tzanis, Sylvie Bonvalot, Sarah Watson, Brent Stockwell, Marcus Conrad, Jessalyn Ubellacker

    Nature　642　(8067)　492-500　2024/04/08

    DOI： 10.21203/rs.3.rs-4165774/v1 　

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    Iron catalyses the oxidation of lipids in biological membranes and promotes a form of cell death called ferroptosis1. Defining where this chemistry occurs in the cell can inform the design of drugs capable of inducing or inhibiting ferroptosis in various disease-relevant settings. Genetic approaches have revealed suppressors of ferroptosis2-4; by contrast, small molecules can provide spatiotemporal control of the chemistry at work5. Here we show that the ferroptosis inhibitor liproxstatin-1 exerts cytoprotective effects by inactivating iron in lysosomes. We also show that the ferroptosis inducer RSL3 initiates membrane lipid oxidation in lysosomes. We designed a small-molecule activator of lysosomal iron-fentomycin-1-to induce the oxidative degradation of phospholipids and ultimately ferroptosis. Fentomycin-1 is able to kill iron-rich CD44high primary sarcoma and pancreatic ductal adenocarcinoma cells, which can promote metastasis and fuel drug tolerance. In such cells, iron regulates cell adaptation6,7 while conferring vulnerability to ferroptosis8,9. Sarcoma cells exposed to sublethal doses of fentomycin-1 acquire a ferroptosis-resistant cell state characterized by the downregulation of mesenchymal markers and the activation of a membrane-damage response. This phospholipid degrader can eradicate drug-tolerant persister cancer cells in vitro and reduces intranodal tumour growth in a mouse model of breast cancer metastasis. Together, these results show that control of iron reactivity confers therapeutic benefits, establish lysosomal iron as a druggable target and highlight the value of targeting cell states10.

  21. Membrane Dynamics and Cation Handling in Ferroptosis International-journal

    Yusuke Hirata, Eikan Mishima

    Physiology　39　(2)　73-87　2024/03/01

    Publisher: American Physiological Society

    DOI： 10.1152/physiol.00029.2023 　

    ISSN： 1548-9213

    eISSN： 1548-9221

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    Ferroptosis, a regulated cell death hallmarked by excessive lipid peroxidation, is implicated in various (patho)physiological contexts. During ferroptosis, lipid peroxidation leads to a diverse change in membrane properties and the dysregulation of ion homeostasis via the cation channels, ultimately resulting in plasma membrane rupture. This review illuminates cellular membrane dynamics and cation handling in ferroptosis regulation.

  22. A tangible method to assess native ferroptosis suppressor activity. International-journal

    Toshitaka Nakamura, Junya Ito, André Santos Dias Mourão, Adam Wahida, Kiyotaka Nakagawa, Eikan Mishima, Marcus Conrad

    Cell reports methods　4　(3)　100710-100710　2024/02/24

    DOI： 10.1016/j.crmeth.2024.100710 　

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    Ferroptosis, a regulated cell death hallmarked by unrestrained lipid peroxidation, plays a pivotal role in the pathophysiology of various diseases, making it a promising therapeutic target. Glutathione peroxidase 4 (GPX4) prevents ferroptosis by reducing (phospho)lipid hydroperoxides, yet evaluation of its actual activity has remained arduous. Here, we present a tangible method using affinity-purified GPX4 to capture a snapshot of its native activity. Next to measuring GPX4 activity, this improved method allows for the investigation of mutational GPX4 activity, exemplified by the GPX4U46C mutant lacking selenocysteine at its active site, as well as the evaluation of GPX4 inhibitors, such as RSL3, as a showcase. Furthermore, we apply this method to the second ferroptosis guardian, ferroptosis suppressor protein 1, to validate the newly identified ferroptosis inhibitor WIN62577. Together, these methods open up opportunities for evaluating alternative ferroptosis suppression mechanisms.

  23. Impact of selenium content in fetal bovine serum on ferroptosis susceptibility and selenoprotein expression in cultured cells.

    Hayato Takashima, Takashi Toyama, Eikan Mishima, Kei Ishida, Yinuo Wang, Atsuya Ichikawa, Junya Ito, Syunsuke Yogiashi, Stephanie Siu, Mayumi Sugawara, Satoru Shiina, Kotoko Arisawa, Marcus Conrad, Yoshiro Saito

    The Journal of toxicological sciences　49　(12)　555-563　2024

    DOI： 10.2131/jts.49.555 　

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    Ferroptosis, a mode of cell death involving iron-dependent lipid peroxidation, has attracted widespread attention in the development of anticancer drugs and toxicological studies as a potential mechanism of chemical-induced cytotoxicity. This process is regulated by several antioxidant enzymes, of which the selenium-containing glutathione peroxidase 4 (GPx4) is the prime regulator. However, accurately and reproducibly evaluating ferroptosis in cultured cells is challenging since numerous experimental factors in in vitro setting can influence the results. In the present study, we found that the expression levels of selenoproteins, such as GPx4 and GPx1, fluctuate across several cell lines depending on the selenium content of different origin of fetal bovine serum (FBS). Cells cultured in FBS containing higher selenium concentrations exhibited elevated GPx4 expression, and were resistant to ferroptosis induced by erastin and RSL3. These findings suggest that the variability of selenium content in different FBS batches can significantly influence the susceptibility of cells to ferroptosis, highlighting the importance of standardizing these factors to enhance the reproducibility of ferroptosis-related experiments.

  24. Integrated chemical and genetic screens unveil FSP1 mechanisms of ferroptosis regulation

    Toshitaka Nakamura, Eikan Mishima, Naoya Yamada, André Santos Dias Mourão, Dietrich Trümbach, Sebastian Doll, Jonas Wanninger, Elena Lytton, Peter Sennhenn, Thamara Nishida Xavier da Silva, José Pedro Friedmann Angeli, Michael Sattler, Bettina Proneth, Marcus Conrad

    Nature Structural & Molecular Biology　2023/11

    DOI： 10.1038/s41594-023-01136-y 　

  25. Changes in Metabolomic Profiles Induced by Switching from an Erythropoiesis-Stimulating Agent to a Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor in Hemodialysis Patients: A Pilot Study

    Kimio Watanabe, Emiko Sato, Eikan Mishima, Shinobu Moriya, Takuma Sakabe, Atsuya Sato, Momoko Fujiwara, Takuya Fujimaru, Yugo Ito, Fumika Taki, Masahiko Nagahama, Kenichi Tanaka, Junichiro James Kazama, Masaaki Nakayama

    International Journal of Molecular Sciences　2023/08/13

    DOI： 10.3390/ijms241612752 　

  26. Changes in Metabolomic Profiles Induced by Switching from an Erythropoiesis-Stimulating Agent to a Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor in Hemodialysis Patients: A Pilot Study

    Kimio Watanabe, Emiko Sato, Eikan Mishima, Shinobu Moriya, Takuma Sakabe, Atsuya Sato, Momoko Fujiwara, Takuya Fujimaru, Yugo Ito, Fumika Taki, Masahiko Nagahama, Kenichi Tanaka, Junichiro James Kazama, Masaaki Nakayama

    International Journal of Molecular Sciences　2023/08

    DOI： 10.3390/ijms241612752 　

  27. Phase separation of FSP1 promotes ferroptosis

    Toshitaka Nakamura, Clara Hipp, André Santos Dias Mourão, Jan Borggräfe, Maceler Aldrovandi, Bernhard Henkelmann, Jonas Wanninger, Eikan Mishima, Elena Lytton, David Emler, Bettina Proneth, Michael Sattler, Marcus Conrad

    Nature　2023/07/13

    DOI： 10.1038/s41586-023-06255-6 　

  28. DHODH inhibitors sensitize to ferroptosis by FSP1 inhibition

    Eikan Mishima, Toshitaka Nakamura, Jiashuo Zheng, Weijia Zhang, André Santos Dias Mourão, Peter Sennhenn, Marcus Conrad

    Nature　2023/07/06

    DOI： 10.1038/s41586-023-06269-0 　

  29. Diverse biological functions of vitamin K: from coagulation to ferroptosis

    Eikan Mishima, Adam Wahida, Tobias Seibt, Marcus Conrad

    Nature Metabolism　2023/06/19

    DOI： 10.1038/s42255-023-00821-y 　

  30. What’s New in the Molecular Mechanisms of Diabetic Kidney Disease: Recent Advances

    Kimio Watanabe, Emiko Sato, Eikan Mishima, Mariko Miyazaki, Tetsuhiro Tanaka

    International Journal of Molecular Sciences　24　(1)　570-570　2022/12/29

    Publisher: MDPI AG

    DOI： 10.3390/ijms24010570 　

    eISSN： 1422-0067

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    Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease, including end-stage kidney disease, and increases the risk of cardiovascular mortality. Although the treatment options for DKD, including angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, sodium-glucose cotransporter 2 inhibitors, and mineralocorticoid receptor antagonists, have advanced, their efficacy is still limited. Thus, a deeper understanding of the molecular mechanisms of DKD onset and progression is necessary for the development of new and innovative treatments for DKD. The complex pathogenesis of DKD includes various different pathways, and the mechanisms of DKD can be broadly classified into inflammatory, fibrotic, metabolic, and hemodynamic factors. Here, we summarize the recent findings in basic research, focusing on each factor and recent advances in the treatment of DKD. Collective evidence from basic and clinical research studies is helpful for understanding the definitive mechanisms of DKD and their regulatory systems. Further comprehensive exploration is warranted to advance our knowledge of the pathogenesis of DKD and establish novel treatments and preventive strategies.

  31. DHODH inhibitors sensitize cancer cells to ferroptosis via FSP1 inhibition

    Eikan Mishima, Toshitaka Nakamura, Jiashuo Zheng, Weijia Zhang, André Santos Dias Mourão, Peter Sennhenn, Marcus Conrad

    2022/10/24

    DOI： 10.21203/rs.3.rs-2190326/v1 　

  32. A non-canonical vitamin K cycle is a potent ferroptosis suppressor. International-journal

    Eikan Mishima, Junya Ito, Zijun Wu, Toshitaka Nakamura, Adam Wahida, Sebastian Doll, Wulf Tonnus, Palina Nepachalovich, Elke Eggenhofer, Maceler Aldrovandi, Bernhard Henkelmann, Ken-Ichi Yamada, Jonas Wanninger, Omkar Zilka, Emiko Sato, Regina Feederle, Daniela Hass, Adriano Maida, André Santos Dias Mourão, Andreas Linkermann, Edward K Geissler, Kiyotaka Nakagawa, Takaaki Abe, Maria Fedorova, Bettina Proneth, Derek A Pratt, Marcus Conrad

    Nature　608　(7924)　778-783　2022/08/03

    DOI： 10.1038/s41586-022-05022-3 　

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    Ferroptosis, a non-apoptotic form of cell death marked by iron-dependent lipid peroxidation1, has a key role in organ injury, degenerative disease and vulnerability of therapy-resistant cancers2. Although substantial progress has been made in understanding the molecular processes relevant to ferroptosis, additional cell-extrinsic and cell-intrinsic processes that determine cell sensitivity toward ferroptosis remain unknown. Here we show that the fully reduced forms of vitamin K-a group of naphthoquinones that includes menaquinone and phylloquinone3-confer a strong anti-ferroptotic function, in addition to the conventional function linked to blood clotting by acting as a cofactor for γ-glutamyl carboxylase. Ferroptosis suppressor protein 1 (FSP1), a NAD(P)H-ubiquinone reductase and the second mainstay of ferroptosis control after glutathione peroxidase-44,5, was found to efficiently reduce vitamin K to its hydroquinone, a potent radical-trapping antioxidant and inhibitor of (phospho)lipid peroxidation. The FSP1-mediated reduction of vitamin K was also responsible for the antidotal effect of vitamin K against warfarin poisoning. It follows that FSP1 is the enzyme mediating warfarin-resistant vitamin K reduction in the canonical vitamin K cycle6. The FSP1-dependent non-canonical vitamin K cycle can act to protect cells against detrimental lipid peroxidation and ferroptosis.

  33. The E2F1-IREB2 axis regulates neuronal ferroptosis in cerebral ischemia. International-journal

    Eikan Mishima

    Hypertension research : official journal of the Japanese Society of Hypertension　45　(6)　1085-1086　2022/06

    DOI： 10.1038/s41440-021-00837-5 　

  34. Nutritional and Metabolic Control of Ferroptosis. International-journal

    Eikan Mishima, Marcus Conrad

    Annual review of nutrition　2022/06/01

    DOI： 10.1146/annurev-nutr-062320-114541 　

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    Ferroptosis is a type of regulated cell death characterized by an excessive lipid peroxidation of cellular membranes caused by the disruption of the antioxidant defense system and/or an imbalanced cellular metabolism. Ferroptosis differentiates from other forms of regulated cell death in that several metabolic pathways and nutritional aspects, including endogenous antioxidants (such as coenzyme Q10, vitamin E, and di/tetrahydrobiopterin), iron handling, energy sensing, selenium utilization, amino acids, and fatty acids, directly regulate the cells' sensitivity to lipid peroxidation and ferroptosis. As hallmarks of ferroptosis have been documented in a variety of diseases, including neurodegeneration, acute organ injury, and therapy-resistant tumors, the modulation of ferroptosis using pharmacological tools or by metabolic reprogramming holds great potential for the treatment of ferroptosis-associated diseases and cancer therapy. Hence, this review focuses on the regulation of ferroptosis by metabolic and nutritional cues and discusses the potential of nutritional interventions for therapy by targeting ferroptosis. Expected final online publication date for the Annual Review of Nutrition, Volume 42 is August 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

  35. Gut Microbiota Dynamics and Uremic Toxins. International-journal

    Eikan Mishima, Takaaki Abe

    Toxins　14　(2)　2022/02/17

    DOI： 10.3390/toxins14020146 　

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    Recent evidence has highlighted the importance of the gut microbiota in the pathophysiology of kidney diseases [...].

  36. SGLT‐1‐specific inhibition ameliorates renal failure and alters the gut microbial community in mice with adenine‐induced renal failure

    Hsin‐Jung Ho, Koichi Kikuchi, Daiki Oikawa, Shun Watanabe, Yoshitomi Kanemitsu, Daisuke Saigusa, Ryota Kujirai, Wakako Ikeda‐Ohtsubo, Mariko Ichijo, Yukako Akiyama, Yuichi Aoki, Eikan Mishima, Yoshiaki Ogata, Yoshitsugu Oikawa, Tetsuro Matsuhashi, Takafumi Toyohara, Chitose Suzuki, Takehiro Suzuki, Nariyasu Mano, Yoshiteru Kagawa, Yuji Owada, Takane Katayama, Toru Nakayama, Yoshihisa Tomioka, Takaaki Abe

    Physiological Reports　9　(24)　2021/12

    Publisher: Wiley

    DOI： 10.14814/phy2.15092 　

    ISSN： 2051-817X

    eISSN： 2051-817X

  37. Fibromuscular dysplasia with recurrence after “long-term” following percutaneous transcatheter renal angioplasty: two case reports with a review of 26 patients

    Shuntaro Oribe, Takafumi Toyohara, Eikan Mishima, Takehiro Suzuki, Koichi Kikuchi, Shun Watanabe, Yoshiaki Morita, Hideki Ota, Kazumasa Seiji, Mariko Miyazaki, Kei Takase, Takaaki Abe

    BMC Nephrology　22　(1)　2021/12

    DOI： 10.1186/s12882-021-02342-w 　

    eISSN： 1471-2369

  38. 血液透析とオンライン血液濾過透析による血中フェノール誘導体,核酸除去率の比較

    島 久登, 道脇 宏行, 三島 英換, 金光 祥臣, 富岡 佳久, 岡田 一義, 阿部 高明, 水口 潤

    日本透析医学会雑誌　54　(Suppl.1)　457-457　2021/05

    Publisher: (一社)日本透析医学会

    ISSN： 1340-3451

    eISSN： 1883-082X

  39. Genetic Background and Clinicopathologic Features of Adult-onset Nephronophthisis. International-journal

    Takuya Fujimaru, Kunio Kawanishi, Takayasu Mori, Eikan Mishima, Akinari Sekine, Motoko Chiga, Masayuki Mizui, Noriaki Sato, Motoko Yanagita, Yuki Ooki, Kiyotaka Nagahama, Yuko Ohnuki, Naoto Hamano, Saki Watanabe, Toshio Mochizuki, Katsushi Nagatsuji, Kenichi Tanaka, Tatsuo Tsukamoto, Hideo Tsushima, Mamiko Shimamoto, Takahiro Tsuji, Tamaki Kuyama, Shinya Kawamoto, Kenji Maki, Ai Katsuma, Mariko Oishi, Kouhei Yamamoto, Shintaro Mandai, Hiroaki Kikuchi, Fumiaki Ando, Yutaro Mori, Koichiro Susa, Soichiro Iimori, Shotaro Naito, Tatemitsu Rai, Junichi Hoshino, Yoshifumi Ubara, Mariko Miyazaki, Michio Nagata, Shinichi Uchida, Eisei Sohara

    Kidney international reports　6　(5)　1346-1354　2021/05

    DOI： 10.1016/j.ekir.2021.02.005 　

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    Introduction: Recently, nephronophthisis (NPH) has been considered a monogenic cause of end-stage renal disease (ESRD) in adults. However, adult-onset NPH is difficult to accurately diagnose and has not been reported in a cohort study. In this study, we assessed the genetic background and clinicopathologic features of adult NPH. Methods: We investigated 18 sporadic adult patients who were suspected as having NPH by renal biopsy. We analyzed 69 genes that cause hereditary cystic kidney disease and compared clinicopathologic findings between patients with and without pathogenic mutations in NPH-causing genes. Results: Seven of 18 patients had pathogenic NPH-causing mutations in NPHP1, NPHP3, NPHP4, or CEP164. Compared with patients without pathogenic mutations, those with pathogenic mutations were significantly younger but did not significantly differ in the classic NPH pathologic findings, such as tubular cysts. On the other hand, the number of tubules with thick tubular basement membrane (TBM) duplication, which was defined as >10-μm thickness, was significantly higher in patients with genetically proven adult NPH than in those without pathogenic mutations. α-Smooth muscle actin (α-SMA)-positive myofibroblasts were detected inside thick TBM duplication. Conclusions: In adult patients with NPH, thick TBM duplication was the specific finding. Our analysis also suggested that older patients tended to have no pathogenic mutations, even when they were suspected to have NPH by renal biopsy. These findings could be the novel clinical clue for the diagnosis of NPH in adult patients.

  40. CE-MS-Based Identification of Uremic Solutes Specific to Hemodialysis Patients International-journal

    Yasutoshi Akiyama, Koichi Kikuchi, Takafumi Toyohara, Eikan Mishima, Chitose Suzuki, Takehiro Suzuki, Masaaki Nakayama, Yoshihisa Tomioka, Tomoyoshi Soga, Takaaki Abe

    Toxins　13　(5)　324-324　2021/04/30

    Publisher: MDPI AG

    DOI： 10.3390/toxins13050324 　

    eISSN： 2072-6651

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    Uremic toxins are suggested to be involved in the pathophysiology of hemodialysis (HD) patients. However, the profile of uremic solutes in HD patients has not been fully elucidated. In this study using capillary electrophoresis mass spectrometry (CE-MS), we comprehensively quantified the serum concentrations of 122 ionic solutes before and after HD in 11 patients. In addition, we compared the results with those in non-HD patients with chronic kidney disease (CKD) to identify HD patient-specific solutes. We identified 38 solutes whose concentrations were higher in pre-HD than in CKD stage G5. Ten solutes among them did not significantly accumulate in non-HD CKD patients, suggesting that these solutes accumulate specifically in HD patients. We also identified 23 solutes whose concentrations were lower in both pre- and post-HD than in CKD stage G5. The serum levels of 14 solutes among them were not affected by renal function in non-HD patients, suggesting that these solutes tend to be lost specifically in HD patients. Our data demonstrate that HD patients have a markedly different profile of serum uremic solute levels compared to that in non-HD CKD patients. The solutes identified in our study may contribute to the pathophysiology of HD patients.

  41. A Novel Mutation in LMX1B (p.Pro219Ala) Causes Focal Segmental Glomerulosclerosis with Alport Syndrome-like Phenotype.

    Yuji Oe, Eikan Mishima, Takayasu Mori, Koji Okamoto, Yohei Honkura, Tasuku Nagasawa, Mai Yoshida, Hiroshi Sato, Jun Suzuki, Ryoukichi Ikeda, Eisei Sohara, Shinichi Uchida, Yukio Katori, Mariko Miyazaki

    Internal medicine (Tokyo, Japan)　60　(18)　2991-2996　2021/04/05

    DOI： 10.2169/internalmedicine.6987-20 　

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    A 69-year-old woman presented with mild renal dysfunction, proteinuria, and sensorineural hearing loss. A renal biopsy showed focal segmental glomerulosclerosis with thinning of the glomerular basement membrane. There was a positive family history of end-stage kidney disease and hearing loss. Although Alport syndrome was suspected from these features, a genetic test using next-generation sequencer identified a novel missense mutation in LMX1B, c.655C>G: p. (Pro219Ala). In silico analyses predicted the pathogenicity of the mutation. Thus, the present case was diagnosed as LMX1B-associated nephropathy presenting with Alport syndrome-like phenotype, expanding the disease spectrum of LMX1B nephropathy.

  42. Effect of uremic toxins on hippocampal cell damage: analysis in vitro and in rat model of chronic kidney disease International-journal

    Kimio Watanabe, Emiko Sato, Eikan Mishima, Mayu Watanabe, Takaaki Abe, Nobuyuki Takahashi, Masaaki Nakayama

    Heliyon　7　(2)　e06221-e06221　2021/02

    Publisher: Elsevier BV

    DOI： 10.1016/j.heliyon.2021.e06221 　

    ISSN： 2405-8440

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    One third of the patients with chronic kidney disease (CKD) develop cognitive impairment, which is also an independent risk factor for mortality. However, the concise mechanism of cerebro-renal interaction has not been clarified. The present study examines the effects of uremic toxins on neuronal cells and analyzes the pathological condition of the brain using mouse hippocampal neuronal HT-22 cells and adenine-induced CKD model rats. Among the uremic toxins analyzed, indoxyl sulfate, indole, 3-indoleacetate, and methylglyoxal significantly decreased viability and glutathione level in HT-22 cells. The mixture of these uremic toxins also decreased viability and glutathione level at a lower dose. Adenine-induced CKD rat showed marked renal damage, increased urinary oxidative stress markers, and increased numbers of pyknotic neuronal cells in hippocampus. CKD rats with damaged hippocampus demonstrated poor learning process when tested using the Morris water maze test. Our results suggest that uremic toxins have a toxic effect on hippocampal neuronal cells and uremic CKD rats shows pyknosis in hippocampus.

  43. Treatment of Refractory Hypertension with Timely Angioplasty in Total Renal Artery Occlusion with Atrophic Kidney.

    Yuri Sasaki, Eikan Mishima, Koichi Kikuchi, Takafumi Toyohara, Takehiro Suzuki, Hideki Ota, Kazumasa Seiji, Mariko Miyazaki, Hideo Harigae, Sadayoshi Ito, Kei Takase, Takaaki Abe

    Internal medicine (Tokyo, Japan)　60　(2)　287-292　2021/01/15

    DOI： 10.2169/internalmedicine.5290-20 　

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    Angioplasty for cases of chronic total occlusion of renal artery with/without atrophic kidney is generally not recommended. We herein report a 57-year-old man who presented with renin-mediated refractory hypertension caused by occlusion of a unilateral renal artery leading to kidney atrophy (length: 69 mm). Angioplasty favorably achieved blood pressure control with normalized renin secretion and enlargement of the atrophic kidney to 85 mm. Timely angioplasty can be beneficial in select patients, even with an atrophic kidney and total occlusion, especially in cases with deterioration of hypertension within six months and the presence of collateral perfusion to the affected kidney.

  44. Kidney enlargement effect of angioplasty for nonatherosclerotic renovascular disease: reversibility of ischemic kidney. International-journal

    Tomoyuki Iwasaki, Eikan Mishima, Takehiro Suzuki, Koichi Kikuchi, Takafumi Toyohara, Kazumasa Seiji, Kei Takase, Mariko Miyazaki, Hideo Harigae, Sadayoshi Ito, Takaaki Abe

    Hypertension research : official journal of the Japanese Society of Hypertension　43　(11)　1214-1221　2020/11

    DOI： 10.1038/s41440-020-0473-6 　

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    Renal artery stenosis causes kidney ischemia, reducing the size of the affected kidney, which eventually results in atrophy. Although renal atrophy is considered irreversible, resolution of the ischemia occasionally restores kidney size when the cause is renal artery stenosis. Angioplasty is effective in patients with nonatherosclerotic renovascular diseases (non-ARVDs). Nevertheless, renal enlargement after angioplasty has not been fully examined. We conducted a retrospective study to examine this phenomenon in non-ARVD patients. Ten patients with a <100-mm pole-to-pole length of the poststenotic kidney were treated with angioplasty. Data were collected up to 12 months after angioplasty. The mean age was 28 years; the estimated glomerular filtration rate was 92 ± 7 mL/min/1.73 m2 (mean ± SEM); blood pressure was 150/99 mmHg; 80% were women; and fibromuscular dysplasia was present in 90% of the patients. All patients had hypertension. The lengths of the poststenotic and contralateral kidney before angioplasty were 91 ± 1 and 111 ± 3 mm, respectively. After angioplasty, the length of the poststenotic kidney gradually increased during the 3 months after treatment (+5.4 mm) and that of the contralateral kidney decreased over the same time course (-3.7 mm). Enlargement was also found in the moderate atrophy subgroup (length < 92 mm), and it was greater in the <30 years old group. In a noteworthy case, renal size in the poststenotic kidney recovered from 87 to 102 mm after angioplasty. Our findings demonstrated that reduced renal size can be reversed after optimal angioplasty in non-ARVD patients, especially young patients, suggesting reversibility of the ischemic kidney.

  45. Germ-Free Conditions Modulate Host Purine Metabolism, Exacerbating Adenine-Induced Kidney Damage. International-journal

    Eikan Mishima, Mariko Ichijo, Takeshi Kawabe, Koichi Kikuchi, Yukako Akiyama, Takafumi Toyohara, Takehiro Suzuki, Chitose Suzuki, Atsuko Asao, Naoto Ishii, Shinji Fukuda, Takaaki Abe

    Toxins　12　(9)　2020/08/26

    DOI： 10.3390/toxins12090547 　

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    Alterations in microbiota are known to affect kidney disease conditions. We have previously shown that germ-free conditions exacerbated adenine-induced kidney damage in mice; however, the mechanism by which this occurs has not been elucidated. To explore this mechanism, we examined the influence of germ-free conditions on purine metabolism and renal immune responses involved in the kidney damage. Germ-free mice showed higher expression levels of purine-metabolizing enzymes such as xanthine dehydrogenase, which converts adenine to a nephrotoxic byproduct 2,8-dihydroxyadenine (2,8-DHA). The germ-free mice also showed increased urinary excretion of allantoin, indicating enhanced purine metabolism. Metabolome analysis demonstrated marked differences in the purine metabolite levels in the feces of germ-free mice and mice with microbiota. Furthermore, unlike the germ-free condition, antibiotic treatment did not increase the expression of purine-metabolizing enzymes or exacerbate adenine-induced kidney damage. Considering renal immune responses, the germ-free mice displayed an absence of renal IL-17A expression. However, the adenine-induced kidney damage in wild-type mice was comparable to that in IL-17A-deficient mice, suggesting that IL-17A does not play a major role in the disease condition. Our results suggest that the enhanced host purine metabolism in the germ-free mice potentially promotes the conversion of the administered adenine into 2,8-DHA, resulting in exacerbated kidney damage. This further suggests a role of the microbiota in regulating host purine metabolism.

  46. The stress specific impact of ALKBH1 on tRNA cleavage and tiRNA generation. International-journal Peer-reviewed

    Sherif Rashad, Xiaobo Han, Kanako Sato, Eikan Mishima, Takaaki Abe, Teiji Tominaga, Kuniyasu Niizuma

    RNA biology　17　(8)　1092-1103　2020/08

    DOI： 10.1080/15476286.2020.1779492 　

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    tiRNAs are small non-coding RNAs produced when tRNA is cleaved under stress. tRNA methylation modifications has emerged in recent years as important regulators for tRNA structural stability and sensitivity to cleavage and tiRNA generation during stress, however, the specificity and higher regulation of such a process is not fully understood. Alkbh1 is a m1A demethylase that leads to destabilization of tRNA and enhanced tRNA cleavage. We examined the impact of Alkbh1 targeting via gene knockdown or overexpression on B35 rat neuroblastoma cell line fate following stresses and on tRNA cleavage. We show that Alkbh1 impact on cell fate and tRNA cleavage is a stress specific process that is impacted by the demethylating capacity of the cellular stress in question. We also show that not all tRNAs are cleaved equally following Alkbh1 manipulation and stress, and that Alkbh1 KD fails to rescue tRNAs from cleavage following demethylating stresses. These findings shed a light on the specificity and higher regulation of tRNA cleavage and should act as a guide for future work exploring the utility of Alkbh1 as a therapeutic target for cancers or ischaemic insult.

  47. HPRT-related hyperuricemia with a novel p.V35M mutation in HPRT1 presenting familial juvenile gout. Peer-reviewed

    Eikan Mishima, Takayasu Mori, Yoko Nakajima, Takafumi Toyohara, Koichi Kikuchi, Yoshitsugu Oikawa, Tetsuro Matsuhashi, Yasuhiro Maeda, Takehiro Suzuki, Masataka Kudo, Sadayoshi Ito, Eisei Sohara, Shinichi Uchida, Takaaki Abe

    CEN case reports　9　(3)　210-214　2020/08

    DOI： 10.1007/s13730-020-00459-9 　

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    Unlike complete deficiency of hypoxanthine phosphoribosyltransferase (HPRT) (i.e., Lesch-Nyhan syndrome), partial HPRT deficiency causes HPRT-related hyperuricemia without neurological symptoms. Herein, we describe a 22-year-old man without neurological symptoms that presented gout, hyperuricemia (serum urate level, 12.2 mg/dL), multiple renal microcalculi, and a family history of juvenile gout that was exhibited by his brother and grandfather. Genetic testing revealed a novel missense mutation, c.103G>A (p.V35M), in the HPRT1 gene, and biochemical testing (conducted using the patient's erythrocytes) showed that the patient retained only 12.4% HPRT enzymatic activity compared to that exhibited by a healthy control subject. We thus diagnosed the patient with HPRT-related hyperuricemia caused by partial HPRT deficiency. After his serum urate level was controlled via treatment with febuxostat, his gout did not recur. Thus, this study emphasizes that HPRT deficiency should be considered as a potential cause of familial juvenile gout, even in the absence of neurological symptoms.

  48. Concurrent analogous organ damage in the brain, eyes, and kidneys in malignant hypertension: reversible encephalopathy, serous retinal detachment, and proteinuria. International-journal Peer-reviewed

    Eikan Mishima, Yukino Funayama, Takehiro Suzuki, Fumiko Mishima, Fumihiko Nitta, Takafumi Toyohara, Koichi Kikuchi, Hiroshi Kunikata, Junichiro Hashimoto, Mariko Miyazaki, Hideo Harigae, Toru Nakazawa, Sadayoshi Ito, Takaaki Abe

    Hypertension research : official journal of the Japanese Society of Hypertension　44　(1)　88-97　2020/07/27

    DOI： 10.1038/s41440-020-0521-2 　

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    Malignant hypertension, a form of hypertensive emergency, causes acute damage in vital organs such as the brain, eyes, and kidneys. We aimed to examine the concurrency of acute hypertensive damage across the target organs to elucidate the underlying analogous pathophysiology. This single-center retrospective study evaluated the characteristics of organ damage, short-term clinical course, and interorgan relationships in patients with malignant hypertension treated between 2008 and 2019. Baseline characteristics of 20 patients who met our inclusion criteria were mean age 48 ± 13 years and blood pressure 222 ± 18/142 ± 16 mmHg; the median estimated glomerular filtration rate and urinary protein level were 49 mL/min/1.73 m2 (interquartile range [IQR] 27-79) and 1.9 g/g creatinine (IQR 0.2-4.0), respectively. Posterior reversible encephalopathy syndrome (PRES) was found in 60% of patients with major involvement and a wide variety of distribution patterns in the brainstem. In the fundus, serous retinal detachment was found in 60% of patients. Patients with PRES and serous retinal detachment showed higher levels of urinary protein than those without symptoms (P = 0.007 and 0.02, respectively), and proteinuria >1 g/g creatinine highly complicated both PRES and serous retinal detachment (91%). Matrix analysis also showed that the three symptoms were highly associated with each other. These results demonstrate the close relationship and concurrency of hypertensive acute organ damage in the brain, eyes, and kidneys. A common analogous mechanism, such as hyperperfusion-induced capillary leakage in each organ, implies an underlying pathophysiology of PRES, serous retinal detachment, and proteinuria.

  49. 尿酸値の失われた遺伝率は、レアバリアントがかなりの部分を説明する

    三澤 計治, 長谷川 嵩矩, 三島 英換, Jutabha Promsuk, 大内 基司, 小島 要, 河合 洋介, 長崎 正朗, 安西 尚彦

    痛風と尿酸・核酸　44　(1)　86-86　2020/07

    Publisher: (一社)日本痛風・尿酸核酸学会

    eISSN： 2435-0095

  50. 尿酸値の失われた遺伝率は、レアバリアントがかなりの部分を説明する

    三澤 計治, 長谷川 嵩矩, 三島 英換, Jutabha Promsuk, 大内 基司, 小島 要, 河合 洋介, 長崎 正朗, 安西 尚彦

    痛風と尿酸・核酸　44　(1)　86-86　2020/07

    Publisher: (一社)日本痛風・尿酸核酸学会

    eISSN： 2435-0095

  51. 血液透析とオンライン血液濾過透析による血中フェノール誘導体、核酸除去率の検討

    島 久登, 道脇 宏行, 金光 祥臣, 三島 英換, 鈴木 千登世, 田尾 知浩, 岡田 一義, 富岡 佳久, 阿部 高明, 水口 潤

    日本腎臓学会誌　62　(4)　351-351　2020/07

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  52. アデニン誘発腎不全マウスにおけるエロビキシバットの効果

    秋山 由雅子, 前川 正充, 金光 祥臣, 菊地 晃一, 何 欣蓉, 三島 英換, 鈴木 健弘, 一條 真梨子, 鈴木 千登世, 眞野 成康, 富岡 佳久, 阿部 高明

    日本腎臓学会誌　62　(4)　337-337　2020/07

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  53. 糖尿病性腎症の発症・進展予測マーカーとしてのフェニル硫酸の有用性

    菊地 晃一, 三枝 大輔, 金光 祥臣, 松本 洋太郎, 三瀬 広記, 中村 智洋, 三島 英換, 豊原 敬文, 鈴木 健弘, 寳澤 篤, 和田 淳, 富岡 佳久, 阿部 高明

    日本腎臓学会誌　62　(4)　276-276　2020/07

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  54. 糖尿病性腎症の発症・進展予測マーカーとしてのフェニル硫酸の有用性

    菊地 晃一, 三枝 大輔, 金光 祥臣, 松本 洋太郎, 三瀬 広記, 中村 智洋, 三島 英換, 豊原 敬文, 鈴木 健弘, 寳澤 篤, 和田 淳, 富岡 佳久, 阿部 高明

    日本腎臓学会誌　62　(4)　276-276　2020/07

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  55. 血液透析とオンライン血液濾過透析による血中フェノール誘導体、核酸除去率の検討

    島 久登, 道脇 宏行, 金光 祥臣, 三島 英換, 鈴木 千登世, 田尾 知浩, 岡田 一義, 富岡 佳久, 阿部 高明, 水口 潤

    日本腎臓学会誌　62　(4)　351-351　2020/07

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  56. アデニン誘発腎不全マウスにおけるエロビキシバットの効果

    秋山 由雅子, 前川 正充, 金光 祥臣, 菊地 晃一, 何 欣蓉, 三島 英換, 鈴木 健弘, 一條 真梨子, 鈴木 千登世, 眞野 成康, 富岡 佳久, 阿部 高明

    日本腎臓学会誌　62　(4)　337-337　2020/07

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  57. Apparent Diffusion Coefficient in the Resolution of Renal Ischemia after Angioplasty on Diffusion-weighted Imaging: Renal Artery Stenosis Caused by Progressive Thrombosis in Residual Chronic Aortic Dissection. Peer-reviewed

    Eikan Mishima, Hideki Ota, Takehiro Suzuki, Takafumi Toyohara, Kazumasa Seiji, Sadayoshi Ito, Yoshikatsu Saiki, Kei Takase, Takaaki Abe

    Internal medicine (Tokyo, Japan)　59　(9)　1173-1177　2020/05/01

    DOI： 10.2169/internalmedicine.3855-19 　

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    We report a case in which diffusion-weighted magnetic resonance imaging (DWI) demonstrated renal artery stenosis-related renal ischemia and the therapeutic efficacy of revascularization. The patient was a 73-year-old man, who underwent descending thoracic aortic replacement due to DeBakey IIIb chronic aortic dissection, and who showed progressive renal dysfunction due to right renal artery stenosis caused by false lumen thrombosis. DWI demonstrated a decreased apparent diffusion coefficient (ADC) in the right kidney, indicating renal ischemia. Angioplasty with stenting restored renal perfusion and improved the renal function, resulting in the normalization of the decreased ADC in the treated kidney. Thus, DWI can be used to monitor renal ischemia in cases involving advanced renal artery stenosis.

  58. Contribution of Rare Variants of the SLC22A12 Gene to the Missing Heritability of Serum Urate Levels. International-journal Peer-reviewed

    Kazuharu Misawa, Takanori Hasegawa, Eikan Mishima, Promsuk Jutabha, Motoshi Ouchi, Kaname Kojima, Yosuke Kawai, Masafumi Matsuo, Naohiko Anzai, Masao Nagasaki

    Genetics　214　(4)　1079-1090　2020/04

    DOI： 10.1534/genetics.119.303006 　

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    Gout is a common arthritis caused by monosodium urate crystals. The heritability of serum urate levels is estimated to be 30-70%; however, common genetic variants account for only 7.9% of the variance in serum urate levels. This discrepancy is an example of "missing heritability." The "missing heritability" suggests that variants associated with uric acid levels are yet to be found. By using genomic sequences of the ToMMo cohort, we identified rare variants of the SLC22A12 gene that affect the urate transport activity of URAT1. URAT1 is a transporter protein encoded by the SLC22A12 gene. We grouped the participants with variants affecting urate uptake by URAT1 and analyzed the variance of serum urate levels. The results showed that the heritability explained by the SLC22A12 variants of men and women exceeds 10%, suggesting that rare variants underlie a substantial portion of the "missing heritability" of serum urate levels.

  59. The guanylate cyclase C agonist linaclotide ameliorates the gut-cardio-renal axis in an adenine-induced mouse model of chronic kidney disease. International-journal Peer-reviewed

    Fumika Nanto-Hara, Yoshitomi Kanemitsu, Shinji Fukuda, Koichi Kikuchi, Kei Asaji, Daisuke Saigusa, Tomoyuki Iwasaki, Hsin-Jung Ho, Eikan Mishima, Takehiro Suzuki, Chitose Suzuki, Tomoya Tsukimi, Tetsuro Matsuhashi, Yoshitsugu Oikawa, Yukako Akiyama, Shigeo Kure, Yuji Owada, Yoshihisa Tomioka, Tomoyoshi Soga, Sadayoshi Ito, Takaaki Abe

    Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association　35　(2)　250-264　2020/02/01

    DOI： 10.1093/ndt/gfz126 　

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    BACKGROUND: Cardiorenal syndrome is a major cause of mortality in patients with chronic kidney disease (CKD). However, the involvement of detrimental humoral mediators in the pathogenesis of cardiorenal syndrome is still controversial. Trimethylamine-N-oxide (TMAO), a hepatic metabolic product of trimethylamine generated from dietary phosphatidylcholine or carnitine derived by the gut microbiota, has been linked directly with progression of cardiovascular disease and renal dysfunction. Thus, targeting TMAO may be a novel strategy for the prevention of cardiovascular disease and chronic kidney disease. METHODS: Linaclotide, a guanylate cyclase C agonist, was administered to adenine-induced renal failure (RF) mice and changes in renal function and levels of gut-derived uremic toxins, as well as the gut microbiota community, were analyzed using metabolomic and metagenomic methods to reveal its cardiorenal effect. RESULTS: Linaclotide decreased the plasma levels of TMAO at a clinically used low dose of 10 μg/kg in the adenine-induced RF mouse model. At a high concentration of 100 μg/kg, linaclotide clearly improved renal function and reduced the levels of various uremic toxins. A reduction in TMAO levels following linaclotide treatment was also observed in a choline-fed pro-atherosclerotic model. Linaclotide ameliorated renal inflammation and fibrosis and cardiac fibrosis, as well as decreased the expression of collagen I, transforming growth factor-β, galectin-3 (Gal-3) and ST2 genes. Plasma levels of Gal-3 and ST2 were also reduced. Because exposure of cardiomyocytes to TMAO increased fibronectin expression, these data suggest that linaclotide reduced the levels of TMAO and various uremic toxins and may result in not only renal, but also cardiac, fibrosis. F4/80-positive macrophages were abundant in small intestinal crypts in RF mice, and this increased expression was decreased by linaclotide. Reduced colonic claudin-1 levels were also restored by linaclotide, suggesting that linaclotide ameliorated the 'leaky gut' in RF mice. Metagenomic analysis revealed that the microbial order Clostridiales could be responsible for the change in TMAO levels. CONCLUSION: Linaclotide reduced TMAO and uremic toxin levels and could be a powerful tool for the prevention and control of the cardiorenal syndrome by modification of the gut-cardio-renal axis.

  60. Drugs Repurposed as Antiferroptosis Agents Suppress Organ Damage, Including AKI, by Functioning as Lipid Peroxyl Radical Scavengers. International-journal Peer-reviewed

    Eikan Mishima, Emiko Sato, Junya Ito, Ken-Ichi Yamada, Chitose Suzuki, Yoshitsugu Oikawa, Tetsuro Matsuhashi, Koichi Kikuchi, Takafumi Toyohara, Takehiro Suzuki, Sadayoshi Ito, Kiyotaka Nakagawa, Takaaki Abe

    Journal of the American Society of Nephrology : JASN　31　(2)　280-296　2020/02

    DOI： 10.1681/ASN.2019060570 　

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    BACKGROUND: Ferroptosis, nonapoptotic cell death mediated by free radical reactions and driven by the oxidative degradation of lipids, is a therapeutic target because of its role in organ damage, including AKI. Ferroptosis-causing radicals that are targeted by ferroptosis suppressors have not been unequivocally identified. Because certain cytochrome P450 substrate drugs can prevent lipid peroxidation via obscure mechanisms, we evaluated their antiferroptotic potential and used them to identify ferroptosis-causing radicals. METHODS: Using a cell-based assay, we screened cytochrome P450 substrate compounds to identify drugs with antiferroptotic activity and investigated the underlying mechanism. To evaluate radical-scavenging activity, we used electron paramagnetic resonance-spin trapping methods and a fluorescence probe for lipid radicals, NBD-Pen, that we had developed. We then assessed the therapeutic potency of these drugs in mouse models of cisplatin-induced AKI and LPS/galactosamine-induced liver injury. RESULTS: We identified various US Food and Drug Administration-approved drugs and hormones that have antiferroptotic properties, including rifampicin, promethazine, omeprazole, indole-3-carbinol, carvedilol, propranolol, estradiol, and thyroid hormones. The antiferroptotic drug effects were closely associated with the scavenging of lipid peroxyl radicals but not significantly related to interactions with other radicals. The elevated lipid peroxyl radical levels were associated with ferroptosis onset, and known ferroptosis suppressors, such as ferrostatin-1, also functioned as lipid peroxyl radical scavengers. The drugs exerted antiferroptotic activities in various cell types, including tubules, podocytes, and renal fibroblasts. Moreover, in mice, the drugs ameliorated AKI and liver injury, with suppression of tissue lipid peroxidation and decreased cell death. CONCLUSIONS: Although elevated lipid peroxyl radical levels can trigger ferroptosis onset, some drugs that scavenge lipid peroxyl radicals can help control ferroptosis-related disorders, including AKI.

  61. Selection of patients for angioplasty for treatment of atherosclerotic renovascular disease: predicting responsive patients. International-journal Peer-reviewed

    Eikan Mishima, Takehiro Suzuki, Sadayoshi Ito

    American journal of hypertension　2020/01/30

    DOI： 10.1093/ajh/hpaa016 　

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    Atherosclerotic renal artery stenosis (ARAS) can cause secondary hypertension, progressive decline in renal function, and cardiac complications. Recent randomized controlled trials including the CORAL study have not reported the benefit of renal artery stenting compared to medical therapy alone to improve renal function or reduce cardiovascular and renal events in the enrolled patients with ARAS. However, observational evidence indicating the benefits of angioplasty in the selected high-risk patients with ARAS has been increasing. Thus, the timely correction of stenosis through angioplasty may have a beneficial effect in selected patients. However, optimal patient selection for angioplasty has been debated and can be challenging at times. Clinicians must identify the responsive patients who would benefit from angioplasty through risk stratification and the prediction of outcomes. Efforts have been made for the determination of predictors that can identify the subgroups of patients who would benefit from angioplasty. Lower age, more severe stenosis, preserved renal perfusion, and absence of diabetes or generalized atherosclerosis have been reported as the predictors for the improvement of hypertension after angioplasty. Global renal ischemia, rapidly declining renal function over 6-12 months, progressive shrinkage of the affected kidney, lower resistive index, and lower levels of albuminuria have been reported as predictors of improved or preserved renal function after angioplasty. This review discusses the identification of ARAS patients who will potentially respond well to angioplasty.

  62. 尿酸値の失われた遺伝率は、レアバリアントがかなりの部分を説明する

    三澤 計治, 長谷川 嵩矩, 三島 英換, Jutabha Promsuk, 大内 基司, 小島 要, 河合 洋介, 長崎 正朗, 安西 尚彦

    日本痛風・核酸代謝学会総会プログラム抄録集　53回　66-66　2020/01

    Publisher: (一社)日本痛風・尿酸核酸学会

  63. Mitochondrial dysfunction underlying sporadic inclusion body myositis is ameliorated by the mitochondrial homing drug MA-5. International-journal

    Yoshitsugu Oikawa, Rumiko Izumi, Masashi Koide, Yoshihiro Hagiwara, Makoto Kanzaki, Naoki Suzuki, Koichi Kikuchi, Tetsuro Matsuhashi, Yukako Akiyama, Mariko Ichijo, Shun Watanabe, Takafumi Toyohara, Takehiro Suzuki, Eikan Mishima, Yasutoshi Akiyama, Yoshiaki Ogata, Chitose Suzuki, Hironori Hayashi, Eiichi N Kodama, Ken-Ichiro Hayashi, Eiji Itoi, Masashi Aoki, Shigeo Kure, Takaaki Abe

    PloS one　15　(12)　e0231064　2020

    DOI： 10.1371/journal.pone.0231064 　

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    Sporadic inclusion body myositis (sIBM) is the most common idiopathic inflammatory myopathy, and several reports have suggested that mitochondrial abnormalities are involved in its etiology. We recruited 9 sIBM patients and found significant histological changes and an elevation of growth differential factor 15 (GDF15), a marker of mitochondrial disease, strongly suggesting the involvement of mitochondrial dysfunction. Bioenergetic analysis of sIBM patient myoblasts revealed impaired mitochondrial function. Decreased ATP production, reduced mitochondrial size and reduced mitochondrial dynamics were also observed in sIBM myoblasts. Cell vulnerability to oxidative stress also suggested the existence of mitochondrial dysfunction. Mitochonic acid-5 (MA-5) increased the cellular ATP level, reduced mitochondrial ROS, and provided protection against sIBM myoblast death. MA-5 also improved the survival of sIBM skin fibroblasts as well as mitochondrial morphology and dynamics in these cells. The reduction in the gene expression levels of Opa1 and Drp1 was also reversed by MA-5, suggesting the modification of the fusion/fission process. These data suggest that MA-5 may provide an alternative therapeutic strategy for treating not only mitochondrial diseases but also sIBM.

  64. Comprehensive and semi-quantitative analysis of carboxyl-containing metabolites related to gut microbiota on chronic kidney disease using 2-picolylamine isotopic labeling LC-MS/MS. International-journal Peer-reviewed

    Yoshitomi Kanemitsu, Eikan Mishima, Masamitsu Maekawa, Yotaro Matsumoto, Daisuke Saigusa, Hiroaki Yamaguchi, Jiro Ogura, Hiroki Tsukamoto, Yoshihisa Tomioka, Takaaki Abe, Nariyasu Mano

    Scientific reports　9　(1)　19075-19075　2019/12/13

    DOI： 10.1038/s41598-019-55600-1 　

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    Carboxyl-containing metabolites, such as bile acids and fatty acids, have many important functions and microbiota is involved in the production of them. In the previous study, we found that the chronic kidney disease (CKD) model mice raised under germ-free conditions provided more severe renal damage than the mice with commensal microbiota. However, the precise influence by the microbiome and carboxyl-containing metabolites to the renal functions is unknown. In this study, we aimed to develop a novel chemical isotope labeling-LC-MS/MS method using the 2-picolylamine and its isotopologue and applied the analysis of effects of microbiome and CKD pathophysiology. The developed semi-quantitative method provided the high accuracy not inferior to the absolute quantification. By comparing of four groups of mice, we found that both microbiota and renal function can alter the composition and level of these metabolites in both plasma and intestine. In particular, the intestinal level of indole-3-acetic acid, short-chain fatty acids and n-3 type of polyunsaturated fatty acid, which play important roles in the endothelial barrier function, were significantly lower in germ-free conditions mice with renal failure. Accordingly, it is suggested these metabolites might have a renoprotective effect on CKD by suppressing epithelial barrier disruption.

  65. tiRNAs as a novel biomarker for cell damage assessment in in vitro ischemia-reperfusion model in rat neuronal PC12 cells. International-journal Peer-reviewed

    Alaa Elkordy, Sherif Rashad, Heba Shehabeldeen, Eikan Mishima, Kuniyasu Niizuma, Takaaki Abe, Teiji Tominaga

    Brain research　1714　8-17　2019/07/01

    DOI： 10.1016/j.brainres.2019.02.019 　

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    The disruption of appropriate cellular stress responses is implicated in the pathogenesis of different neurological disorders including ischemic injury. Early diagnosis and treatment are often associated with better prognosis in ischemic stroke patients. Thus, there is an urgent need to improve the speed and accuracy of stroke diagnosis by developing highly sensitive stroke biomarkers. We recently reported that transfer RNA (tRNA) was involved in cell stress response pathways. Under cell stress conditions, mature tRNA is cleaved by a specific ribonuclease, angiogenin, generating tRNA-derived stress-induced RNA (tiRNA). To study tiRNA generation in an in vitro model of ischemic-reperfusion injury, we used the rat neuronal cell line, PC12, in combination with analysis of SYBR staining and immuno-northern blotting using anti-1-methyladenosine antibody, which detects 1-methyladenosine (m1A) modification of tRNA. We demonstrated that oxygen-glucose deprivation induced tRNA cleavage and tiRNA generation. Time course analysis showed a dramatic up-regulation of tiRNA generation by oxygen-glucose deprivation (OGD) which started a few minutes after reperfusion. Minocycline, a neuroprotective antibiotic, treatment protected PC12 cells against OGD-reperfusion cell damage resulting in a marked down-regulation of the generated tiRNA. Our findings show that cleavage of tRNA and tiRNA generation in rat neuronal PC12 cells occurs with reperfusion injury and the detection of tiRNA could be used as a potential cell damage marker and treatment effect indicator for this type of injury.

  66. ケモカインレセプターCCR10阻害薬による腎不全抑制効果の検討

    一條 真梨子, 何 欣蓉, 金光 祥臣, 菊地 晃一, 秋山 由雅子, 三島 英換, 鈴木 健弘, 鈴木 千登世, 富岡 佳久, 伊藤 貞嘉, 阿部 高明

    日本腎臓学会誌　61　(3)　325-325　2019/05

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  67. Gut microbiome-derived phenyl sulfate contributes to albuminuria in diabetic kidney disease. International-journal Peer-reviewed

    Koichi Kikuchi, Daisuke Saigusa, Yoshitomi Kanemitsu, Yotaro Matsumoto, Paxton Thanai, Naoto Suzuki, Koki Mise, Hiroaki Yamaguchi, Tomohiro Nakamura, Kei Asaji, Chikahisa Mukawa, Hiroki Tsukamoto, Toshihiro Sato, Yoshitsugu Oikawa, Tomoyuki Iwasaki, Yuji Oe, Tomoya Tsukimi, Noriko N Fukuda, Hsin-Jung Ho, Fumika Nanto-Hara, Jiro Ogura, Ritsumi Saito, Shizuko Nagao, Yusuke Ohsaki, Satoshi Shimada, Takehiro Suzuki, Takafumi Toyohara, Eikan Mishima, Hisato Shima, Yasutoshi Akiyama, Yukako Akiyama, Mariko Ichijo, Tetsuro Matsuhashi, Akihiro Matsuo, Yoshiaki Ogata, Ching-Chin Yang, Chitose Suzuki, Matthew C Breeggemann, Jurgen Heymann, Miho Shimizu, Susumu Ogawa, Nobuyuki Takahashi, Takashi Suzuki, Yuji Owada, Shigeo Kure, Nariyasu Mano, Tomoyoshi Soga, Takashi Wada, Jeffrey B Kopp, Shinji Fukuda, Atsushi Hozawa, Masayuki Yamamoto, Sadayoshi Ito, Jun Wada, Yoshihisa Tomioka, Takaaki Abe

    Nature communications　10　(1)　1835-1835　2019/04/23

    DOI： 10.1038/s41467-019-09735-4 　

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    Diabetic kidney disease is a major cause of renal failure that urgently necessitates a breakthrough in disease management. Here we show using untargeted metabolomics that levels of phenyl sulfate, a gut microbiota-derived metabolite, increase with the progression of diabetes in rats overexpressing human uremic toxin transporter SLCO4C1 in the kidney, and are decreased in rats with limited proteinuria. In experimental models of diabetes, phenyl sulfate administration induces albuminuria and podocyte damage. In a diabetic patient cohort, phenyl sulfate levels significantly correlate with basal and predicted 2-year progression of albuminuria in patients with microalbuminuria. Inhibition of tyrosine phenol-lyase, a bacterial enzyme responsible for the synthesis of phenol from dietary tyrosine before it is metabolized into phenyl sulfate in the liver, reduces albuminuria in diabetic mice. Together, our results suggest that phenyl sulfate contributes to albuminuria and could be used as a disease marker and future therapeutic target in diabetic kidney disease.

  68. Renin-angiotensin system inhibitors in hypertensive adults with non-diabetic CKD with or without proteinuria: a systematic review and meta-analysis of randomized trials. International-journal Peer-reviewed

    Eikan Mishima, Yoshisuke Haruna, Hisatomi Arima

    Hypertension research : official journal of the Japanese Society of Hypertension　42　(4)　469-482　2019/04

    DOI： 10.1038/s41440-018-0116-3 　

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    The efficacy and safety of renin-angiotensin system inhibitors (RAS-I) in hypertensive adults with non-diabetic chronic kidney disease (CKD) differ depending on the presence or the absence of proteinuria. To estimate the effects of RAS-I in this population, we performed a systematic review and meta-analysis of randomized controlled trials where treatment with angiotensin-converting-enzyme inhibitors or angiotensin II receptor blockers were compared with placebo or active controls in adults with non-diabetic CKD. The treatment effects were separately reviewed in patients with and without proteinuria. Based on a search of Medline and the Cochrane Library up to September 2017, we identified 42 eligible trials (28, proteinuria-positive group; 6, proteinuria-negative group; 2, mixed-proteinuria group; and 6, proteinuria data-unavailable group). RAS-I reduced renal failure events in comparison to placebo or active agents in the proteinuria-positive group (relative risk [RR] 0.63, 95% confidence interval [CI] 0.52-0.75), but showed no significant effects on renal failure risk in the proteinuria-negative group (RR 0.64, 95% CI 0.18-2.30) although it reduced microalbuminuria. For cardiovascular events, RAS-I was not associated with a significantly reduced risk in both the proteinuria-positive and proteinuria-negative group (RR 0.77 and 1.06, 95% CI 0.51-1.16 and 0.85-1.32, respectively). In the mixed-proteinuria group and proteinuria data-unavailable group, RAS-I showed no significant effects on renal and cardiovascular events. Among adverse events, hyperkalemia increased with RAS-I administration in the proteinuria-positive group (RR 2.01, 95% CI 1.07-3.77). Our analysis showed the renoprotective effects of RAS-I treatment in patients with non-diabetic CKD having proteinuria, supporting its use as the first-line antihypertensive therapy in this population.

  69. Immuno-Northern Blotting: Detection of Modified RNA Using Gel Separation and Antibodies to Modified Nucleosides. International-journal Peer-reviewed

    Eikan Mishima, Takaaki Abe

    Methods in molecular biology (Clifton, N.J.)　1870　179-187　2019

    DOI： 10.1007/978-1-4939-8808-2_13 　

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    Immuno-northern blotting is a method for detecting modified RNAs using gel separation and specific antibodies to modified nucleosides. This method was developed by combining two commonly used molecular biology techniques: western blotting and northern blotting. In this method, urea-polyacrylamide (or agarose) gel-separated RNAs are transferred to positively charged nylon membrane and then immune detection is performed with specific antibodies to modified nucleosides: such as 1-methyladenosine, N6-methyladenosine, and pseudouridine. This highly sensitive and relatively simple method, which uses widely available laboratory equipment, enables small laboratories to compare the abundance of modified nucleic acids across samples.

  70. Low frequency of cervicocranial artery involvement in Japanese with renal artery fibromuscular dysplasia compared with that of Caucasians. Peer-reviewed

    Eikan Mishima, Shu Umezawa, Takehiro Suzuki, Miki Fujimura, Michiaki Abe, Junichiro Hashimoto, Takaaki Abe, Sadayoshi Ito

    Clinical and experimental nephrology　22　(6)　1294-1299　2018/12

    DOI： 10.1007/s10157-018-1575-1 　

    ISSN： 1342-1751

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    BACKGROUND: Fibromuscular dysplasia (FMD), which usually affects the renal artery, also affects the carotid, vertebral, and intracranial arteries. Previous studies have shown a high prevalence of concomitant renal artery and cervicocranial lesions in FMD patients. However, the analyzed subjects were mostly Caucasians in Western countries. METHOD: We performed a retrospective analysis to examine the prevalence of cervicocranial vascular lesions in Japanese FMD patients with renal artery involvement at a single institution. The presence of cervicocranial lesions was evaluated by Doppler echography and magnetic resonance angiography. We compared this prevalence with that reported in the literature. RESULT: Thirty-one Japanese FMD patients with renal artery lesions were studied. The mean age was 30 ± 12 years, 71% were women, and 16% were smokers; all patients were Asians and had hypertension. Multifocal, tubular, and unifocal types of renal lesions were found in 52, 35, and 13% of patients, respectively. Bilateral renal lesions were found in 13% of patients. None of the patients had a cervical vascular lesion associated with FMD. Only two patients (8%) had a lesion in the intracranial artery, of which one was a known case of moyamoya disease. CONCLUSION: These findings suggest that cervical artery involvement and intracranial artery involvement are not common in renal FMD patients in Japan, which is in contrast to the data reported for Caucasian patients in Western countries. Ethnic differences could influence the occurrence of cervicocranial lesions. A study with a larger sample size should be performed to validate these findings.

  71. Canagliflozin reduces plasma uremic toxins and alters the intestinal microbiota composition in a chronic kidney disease mouse model International-journal Peer-reviewed

    †Mishima, E, †Fukuda, S, Contributed equally to this work, Kanemitsu, Y, Saigusa, D, Mukawa, C, Asaji, K, Matsumoto, Y, Tsukamoto, H, Tachikawa, T, Tsukimi, T, Fukuda, N, Ho, HJ., Kikuchi, K. Suzuki, C, Nanto, F, Suzuki, T, Ito, S, Soga, T, Tomioka, Y, Abe, T

    Am. J. Physiol. Renal. Physiol.　315　(4)　F824-F833-F833　2018/10/01

    Publisher: American Journal of Physiology - Renal Physiology

    DOI： 10.1152/ajprenal.00314.2017 　

    ISSN： 0363-6127

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    © 2018 the American Physiological Society. Mishima E, Fukuda S, Kanemitsu Y, Saigusa D, Mukawa C, Asaji K, Matsumoto Y, Tsukamoto H, Tachikawa T, Tsukimi T, Fukuda NN, Ho HJ, Kikuchi K, Suzuki C, Nanto F, Suzuki T, Ito S, Soga T, Tomioka Y, Abe T. Canagliflozin reduces plasma uremic toxins and alters the intestinal microbiota composition in a chronic kidney disease mouse model. Am J Physiol Renal Physiol 315: F824–F833, 2018. First published November 22, 2017; doi:10.1152/ajprenal.00314.2017.—Accumulation of uremic toxins, which exert deleterious effects in chronic kidney disease, is influenced by the intestinal environment; the microbiota contributes to the production of representative uremic toxins, including p-cresyl sulfate and indoxyl sulfate. Canagliflozin is a sodium-glucose cotransporter (SGLT) 2 inhibitor, and it also exerts a modest inhibitory effect on SGLT1. The inhibition of intestinal SGLT1 can influence the gastrointestinal environment. We examined the effect of canagliflozin on the accumulation of uremic toxins in chronic kidney disease using adenine-induced renal failure mice. Two-week canagliflozin (10 mg/kg po) treatment did not influence the impaired renal

  72. Canagliflozin reduces plasma uremic toxins and alters the intestinal microbiota composition in a chronic kidney disease mouse model. International-journal Peer-reviewed

    Mishima E, Fukuda S, Kanemitsu Y, Saigusa D, Mukawa C, Asaji K, Matsumoto Y, Tsukamoto H, Tachikawa T, Tsukimi T, Fukuda NN, Ho HJ, Kikuchi K, Suzuki C, Nanto F, Suzuki T, Ito S, Soga T, Tomioka Y, Abe T

    American journal of physiology. Renal physiology　315　(4)　F824-F833　2018/10

    DOI： 10.1152/ajprenal.00314.2017 　

    ISSN： 1931-857X

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    Accumulation of uremic toxins, which exert deleterious effects in chronic kidney disease, is influenced by the intestinal environment; the microbiota contributes to the production of representative uremic toxins, including p-cresyl sulfate and indoxyl sulfate. Canagliflozin is a sodium-glucose cotransporter (SGLT) 2 inhibitor, and it also exerts a modest inhibitory effect on SGLT1. The inhibition of intestinal SGLT1 can influence the gastrointestinal environment. We examined the effect of canagliflozin on the accumulation of uremic toxins in chronic kidney disease using adenine-induced renal failure mice. Two-week canagliflozin (10 mg/kg po) treatment did not influence the impaired renal function; however, it significantly reduced the plasma levels of p-cresyl sulfate and indoxyl sulfate in renal failure mice (a 75% and 26% reduction, respectively, compared with the vehicle group). Additionally, canagliflozin significantly increased cecal short-chain fatty acids in the mice, suggesting the promotion of bacterial carbohydrate fermentation in the intestine. Analysis of the cecal microbiota showed that canagliflozin significantly altered microbiota composition in the renal failure mice. These results indicate that canagliflozin exerts intestinal effects that reduce the accumulation of uremic toxins including p-cresyl sulfate. Reduction of accumulated uremic toxins by canagliflozin could provide a potential therapeutic option in chronic kidney disease.

  73. Stress-induced tRNA cleavage and tiRNA generation in rat neuronal PC12 cells. International-journal Peer-reviewed

    Alaa Elkordy, Eikan Mishima, Kuniyasu Niizuma, Yasutoshi Akiyama, Miki Fujimura, Teiji Tominaga, Takaaki Abe

    Journal of neurochemistry　146　(5)　560-569　2018/09

    DOI： 10.1111/jnc.14321 　

    ISSN： 0022-3042

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    Transfer RNA (tRNA) plays a role in stress response programs involved in various pathological conditions including neurological diseases. Under cell stress conditions, intracellular tRNA is cleaved by a specific ribonuclease, angiogenin, generating tRNA-derived fragments or tRNA-derived stress-induced RNA (tiRNA). Generated tiRNA contributes to the cell stress response and has potential cell protective effects. However, tiRNA generation under stress conditions in neuronal cells has not been fully elucidated. To examine angiogenin-mediated tiRNA generation in neuronal cells, we used the rat neuronal cell line, PC12, in combination with analysis of SYBR staining and immuno-northern blotting using anti-1-methyladenosine antibody, which specifically and sensitively detects tiRNA. Oxidative stress induced by arsenite and hydrogen peroxide caused tRNA cleavage and tiRNA generation in PC12 cells. We also demonstrated that oxygen-glucose deprivation, which is an in vitro model of ischemic-reperfusion injury, induced tRNA cleavage and tiRNA generation. In these stress conditions, the amount of generated tiRNA was associated with the degree of morphological cell damage. Time course analysis indicated that generation of tiRNA was prior to severe cell damage and cell death. Angiogenin over-expression did not influence the amount of tiRNA in normal culture conditions; however, it significantly increased tiRNA generation induced by cell stress conditions. Our findings show that angiogenin-mediated tiRNA generation can be induced in neuronal cells by different cell stressors, including ischemia-reperfusion. Additionally, detection of tiRNA could be used as a potential cell damage marker in neuronal cells. Cover Image for this issue: doi: 10.1111/jnc.14191.

  74. グアニル酸シクラーゼC受容体作動薬リナクロチドは腎不全に伴う腸内環境悪性化を改善し腎線維化を抑制する

    南都 文香, 福田 真嗣, 金光 祥臣, 三枝 大輔, 菊地 晃一, 何 欣蓉, 三島 英換, 鈴木 健弘, 松橋 徹郎, 及川 義嗣, 鈴木 千登世, 富岡 佳久, 曽我 朋義, 伊藤 貞嘉, 阿部 高明

    日本腎臓学会誌　60　(3)　463-463　2018/04

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  75. Renovascular hypertension associated with JAK2 V617F positive myeloproliferative neoplasms treated with angioplasty: 2 cases and literature review. International-journal Peer-reviewed

    Eikan Mishima, Takehiro Suzuki, Yoichi Takeuchi, Kazumasa Seiji, Noriko Fukuhara, Kei Takase, Hideo Harigae, Takaaki Abe, Sadayoshi Ito

    Journal of clinical hypertension (Greenwich, Conn.)　20　(4)　798-804　2018/04

    DOI： 10.1111/jch.13257 　

    ISSN： 1524-6175

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    Myeloproliferative neoplasms (MPNs) with Janus kinase 2 (JAK2) mutation are associated with a high risk for occlusive vascular diseases. We report 2 cases of renovascular hypertension associated with JAK2 V617F mutation-positive MPNs and provide a literature review. In Case 1, a 63-year-old woman had resistant hypertension, massive proteinuria, and erythrocytosis. Evaluations revealed right renal artery stenosis causing renovascular hypertension and polycythemia vera with JAK2 V617F mutation. Renin-angiotensin system inhibitors and subsequent angioplasty controlled the blood pressure and the proteinuria resolved. In Case 2, a 74-year-old woman had resistant hypertension and thrombocytosis. Evaluations confirmed left renal artery stenosis and essential thrombocythemia with JAK2 V617F. Angioplasty cured the hypertension. A literature review of 18 cases revealed the following as the most common characteristics of MPN-associated renovascular hypertension: manifests primarily in women; is associated with untreated polycythemia vera and essential thrombocythemia, concomitant leukocytosis, and JAK2 mutation positivity; and is responsive to angioplasty. This report demonstrates that JAK2 mutation-positive MPNs are a less common but important underlying cause of adult renovascular hypertension.

  76. Focal Segmental Glomerulosclerosis Associated with Chronic Progressive External Ophthalmoplegia and Mitochondrial DNA A3243G Mutation. International-journal Peer-reviewed

    Kaori Narumi, Eikan Mishima, Yukako Akiyama, Tetsuro Matsuhashi, Takashi Nakamichi, Kiyomi Kisu, Shuhei Nishiyama, Hajime Ikenouchi, Akio Kikuchi, Rumiko Izumi, Mariko Miyazaki, Takaaki Abe, Hiroshi Sato, Sadayoshi Ito

    Nephron　138　(3)　243-248　2018

    DOI： 10.1159/000485109 　

    ISSN： 1660-8151

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    Focal segmental glomerulosclerosis (FSGS) is caused by various etiologies, with mitochondrial dysfunction being one of the causes. FSGS is known to be associated with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), which is a subclass of mitochondrial disease. However, it has rarely been reported in other mitochondrial disease subclasses. Here, we reported a 20-year-old man diagnosed with FSGS associated with chronic progressive external ophthalmoplegia (CPEO) due to mitochondrial DNA (mtDNA) 3243A>G mutation. He presented with left ptosis, short stature, mild sensorineural deafness, and cardiac conduction block. A renal biopsy sample showed segmental sclerosis and adhesions between capillaries and Bowman's capsule, indicating FSGS. Electron microscopy demonstrated abnormal aggregated mitochondria in podocytes, and the basement membrane and epithelial cells of Bowman's capsule. Skeletal muscle biopsy also showed accumulation of abnormal mitochondria. mtDNA analysis identified heteroplasmic mtDNA 3243A>G mutation with no large-scale deletions. From these findings, we diagnosed the case as CPEO with multi-organ involvement including FSGS. Our report demonstrates that CPEO, as well as MELAS, can be associated with FSGS. Because mitochondrial disease presents with a variety of clinical symptoms, atypical cases with non-classical manifestations are observed. Thus, mitochondrial disease should be considered as an underlying cause of FSGS with systemic manifestations even with atypical phenotypes.

  77. Impact of the Oral Adsorbent AST-120 on Organ-Specific Accumulation of Uremic Toxins: LC-MS/MS and MS Imaging Techniques. International-journal Peer-reviewed

    Emiko Sato, Daisuke Saigusa, Eikan Mishima, Taeko Uchida, Daisuke Miura, Tomomi Morikawa-Ichinose, Kiyomi Kisu, Akiyo Sekimoto, Ritsumi Saito, Yuji Oe, Yotaro Matsumoto, Yoshihisa Tomioka, Takefumi Mori, Nobuyuki Takahashi, Hiroshi Sato, Takaaki Abe, Toshimitsu Niwa, Sadayoshi Ito

    Toxins　10　(1)　2017/12/28

    DOI： 10.3390/toxins10010019 　

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    Elevated circulating uremic toxins are associated with a variety of symptoms and organ dysfunction observed in patients with chronic kidney disease (CKD). Indoxyl sulfate (IS) and p-cresyl sulfate (PCS) are representative uremic toxins that exert various harmful effects. We recently showed that IS induces metabolic alteration in skeletal muscle and causes sarcopenia in mice. However, whether organ-specific accumulation of IS and PCS is associated with tissue dysfunction is still unclear. We investigated the accumulation of IS and PCS using liquid chromatography/tandem mass spectrometry in various tissues from mice with adenine-induced CKD. IS and PCS accumulated in all 15 organs analyzed, including kidney, skeletal muscle, and brain. We also visualized the tissue accumulation of IS and PCS with immunohistochemistry and mass spectrometry imaging techniques. The oral adsorbent AST-120 prevented some tissue accumulation of IS and PCS. In skeletal muscle, reduced accumulation following AST-120 treatment resulted in the amelioration of renal failure-associated muscle atrophy. We conclude that uremic toxins can accumulate in various organs and that AST-120 may be useful in treating or preventing organ dysfunction in CKD, possibly by reducing tissue accumulation of uremic toxins.

  78. A novel indole compound MA-35 attenuates renal fibrosis by inhibiting both TNF-α and TGF-β1 pathways Peer-reviewed

    Hisato Shima, Kensuke Sasaki, Takehiro Suzuki, Chikahisa Mukawa, Ten Obara, Yuki Oba, Akihiro Matsuo, Takayasu Kobayashi, Eikan Mishima, Shun Watanabe, Yasutoshi Akiyama, Koichi Kikuchi, Tetsuro Matsuhashi, Yoshitsugu Oikawa, Fumika Nanto, Yukako Akiyama, Hsin-Jung Ho, Chitose Suzuki, Daisuke Saigusa, Atsushi Masamune, Yoshihisa Tomioka, Takao Masaki, Sadayoshi Ito, Ken-Ichiro Hayashi, Takaaki Abe

    Scientific Reports　7　(1)　2017/12/01

    DOI： 10.1038/s41598-017-01702-7 　

    ISSN： 2045-2322

  79. Inherited, not acquired, Gitelman syndrome in a patient with Sjögren's syndrome: importance of genetic testing to distinguish the two forms. Peer-reviewed

    Mishima E, Mori T, Sohara E, Uchida S, Abe T, Ito S

    CEN case reports　6　(2)　180-184　2017/11

    DOI： 10.1007/s13730-017-0271-4 　

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    Gitelman syndrome (GS) is an autosomal recessive, salt-losing renal tubulopathy caused by mutations in the SLC12A3 gene; however, it can also be acquired in patients with autoimmune disease, especially in those with Sjögren's syndrome. Differentiating between the inherited and acquired forms of GS is clinically difficult. We report a case of inherited, not acquired, GS in a patient with Sjögren's syndrome. A 41-year-old woman, who had been diagnosed with Sjögren's syndrome at 27-years-old, had shown chronic hypokalemia (2.5-3.5 mmol/L). Laboratory tests showed hypokalemic alkalosis, hypomagnesemia, and hypocalciuria, corresponding to GS. Although acquired GS associated with Sjögren's syndrome was initially suspected, a genetic test identified a novel homozygous mutation of c.1336-2A > T in the SLC12A3 gene, which resulted in aberrant splicing in the SLC12A3 transcript with the exclusion of exons 11 and 12. Thus, the GS was diagnosed as not the acquired but the inherited form. In the diagnosis of GS in patients with autoimmune disease, genetic testing of SLC12A3 is essential for differentiating the two forms.

  80. Selective embolization therapy for intrarenal artery stenosis causing renovascular hypertension: Efficacy and follow-up renal imaging Peer-reviewed

    Eikan Mishima, Takehiro Suzuki, Kazumasa Seiji, Yasutoshi Akiyama, Hideki Ota, Junichiro Hashimoto, Kei Takase, Takaaki Abe, Sadayoshi Ito

    JOURNAL OF CLINICAL HYPERTENSION　19　(10)　1028-1031　2017/10

    DOI： 10.1111/jch.13040 　

    ISSN： 1524-6175

    eISSN： 1751-7176

  81. Evaluation of the impact of gut microbiota on uremic solute accumulation by a CE-TOFMS-based metabolomics approach Peer-reviewed

    Eikan Mishima, Shinji Fukuda, Chikahisa Mukawa, Akinori Yuri, Yoshitomi Kanemitsu, Yotaro Matsumoto, Yasutoshi Akiyama, Noriko N. Fukuda, Hiroki Tsukamoto, Kei Asaji, Hisato Shima, Koichi Kikuchi, Chitose Suzuki, Takehiro Suzuki, Yoshihisa Tomioka, Tomoyoshi Soga, Sadayoshi Ito, Takaaki Abe

    KIDNEY INTERNATIONAL　92　(3)　634-645　2017/09

    DOI： 10.1016/j.kint.2017.02.011 　

    ISSN： 0085-2538

    eISSN： 1523-1755

  82. Potential Drug Interactions Mediated by Renal Organic Anion Transporter OATP4C1 Peer-reviewed

    Toshihiro Sato, Eikan Mishima, Nariyasu Mano, Takaaki Abe, Hiroaki Yamaguchi

    JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS　362　(2)　271-277　2017/08

    DOI： 10.1124/jpet.117.241703 　

    ISSN： 0022-3565

    eISSN： 1521-0103

  83. 'Lead pipe'-like stiff aorta with grossly widened pulse pressure in burned-out Takayasu arteritis Peer-reviewed

    Eikan Mishima, Takehiro Suzuki, Junichiro Hashimoto, Takaaki Abe, Sadayoshi Ito

    EUROPEAN HEART JOURNAL-CARDIOVASCULAR IMAGING　18　(7)　819-819　2017/07

    DOI： 10.1093/ehjci/jex047 　

    ISSN： 2047-2404

    eISSN： 2047-2412

  84. Mitochonic Acid 5 (MA-5) Facilitates ATP Synthase Oligomerization and Cell Survival in Various Mitochondrial Diseases Peer-reviewed

    Tetsuro Matsuhashi, Takeya Sato, Shin-ichiro Kanno, Takehiro Suzuki, Akihiro Matsuo, Yuki Oba, Motoi Kikusato, Emi Ogasawara, Tai Kudo, Kosuke Suzuki, Osamu Ohara, Hiroko Shimbo, Fumika Nanto, Hiroaki Yamaguchi, Daisuke Saigusa, Yasuno Mukaiyama, Akiko Watabe, Koichi Kikuchi, Hisato Shima, Eikan Mishima, Yasutoshi Akiyama, Yoshitsugu Oikawa, Hsin-Jung Ho, Yukako Akiyama, Chitose Suzuki, Mitsugu Uematsu, Masaki Ogata, Naonori Kumagai, Masaaki Toyomizu, Atsushi Hozawa, Nariyasu Mano, Yuji Owada, Setsuya Aiba, Teruyuki Yanagisawa, Yoshihisa Tomioka, Shigeo Kure, Sadayoshi Ito, Kazuto Nakada, Ken-ichiro Hayashi, Hitoshi Osaka, Takaaki Abe

    EBIOMEDICINE　20　27-38　2017/06

    DOI： 10.1016/j.ebiom.2017.05.016 　

    ISSN： 2352-3964

  85. 著明な脈圧増大を伴う鉛管様大動脈と多発動脈狭窄を呈する陳旧性高安動脈炎の1例

    三島 英換, 鈴木 健弘, 橋本 潤一郎, 阿部 高明, 伊藤 貞嘉

    日本高血圧学会臨床高血圧フォーラムプログラム・抄録集　6回　177-177　2017/05

    Publisher: (NPO)日本高血圧学会

  86. Indoxyl Sulfate(IS)のヒトポドサイトに対する影響

    鈴木 康介, 大庭 悠貴, 菊地 晃一, 松橋 徹郎, 島 久登, 三島 英換, 鈴木 千登世, 鈴木 健弘, 阿部 祥英, 阿部 高明

    日本腎臓学会誌　59　(3)　303-303　2017/04

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  87. たこつぼ心筋症の病態形成における発症前からの潜在的心筋虚血の進行 発症前後の心電図変化を捉えた1例から

    三島 英換, 橋本 潤一郎, 竹内 陽一, 長澤 将, 阿部 高明, 伊藤 貞嘉

    日本内分泌学会雑誌　92　(3)　902-902　2017/01

    Publisher: (一社)日本内分泌学会

    ISSN： 0029-0661

    eISSN： 2186-506X

  88. Acute Kidney Injury from Excessive Potentiation of Calcium-channel Blocker via Synergistic CYP3A4 Inhibition by Clarithromycin Plus Voriconazole Peer-reviewed

    Eikan Mishima, Kazuichi Maruyama, Toru Nakazawa, Takaaki Abe, Sadayoshi Ito

    INTERNAL MEDICINE　56　(13)　1687-1690　2017

    DOI： 10.2169/internalmedicine.56.8313 　

    ISSN： 0918-2918

    eISSN： 1349-7235

  89. Metabolic alterations by indoxyl sulfate in skeletal muscle induce uremic sarcopenia in chronic kidney disease Peer-reviewed

    Emiko Sato, Takefumi Mori, Eikan Mishima, Arisa Suzuki, Sanae Sugawara, Naho Kurasawa, Daisuke Saigusa, Daisuke Miura, Tomomi Morikawa-Ichinose, Ritsumi Saito, Ikuko Oba-Yabana, Yuji Oe, Kiyomi Kisu, Eri Naganuma, Kenji Koizumi, Takayuki Mokudai, Yoshimi Niwano, Tai Kudo, Chitose Suzuki, Nobuyuki Takahashi, Hiroshi Sato, Takaaki Abe, Toshimitsu Niwa, Sadayoshi Ito

    SCIENTIFIC REPORTS　6　36618　2016/11

    DOI： 10.1038/srep36618 　

    ISSN： 2045-2322

  90. Prelude to Takotsubo cardiomyopathy: subclinical progression of antecedent myocardial ischaemia prior to symptom onset Peer-reviewed

    Eikan Mishima, Yoichi Takeuchi, Tasuku Nagasawa, Junichiro Hashimoto

    EUROPEAN HEART JOURNAL　37　(37)　2845-2845　2016/10

    DOI： 10.1093/eurheartj/ehw216 　

    ISSN： 0195-668X

    eISSN： 1522-9645

  91. PTRA施行困難な分枝型腎血管性高血圧の治療オプションとしての選択的腎動脈塞栓術の有用性

    新沢 賢樹, 三島 英換, 鈴木 健弘, 菊地 晃一, 島 久登, 清治 和将, 高瀬 圭, 阿部 高明, 伊藤 貞嘉

    日本高血圧学会総会プログラム・抄録集　39回　390-390　2016/09

    Publisher: (NPO)日本高血圧学会

  92. わずかな領域の腎虚血が高血圧の原因となった分枝型腎血管性高血圧の1例 高血圧の病態形成に限局性腎虚血が与える影響

    三島 英換, 鈴木 健弘, 菊地 晃一, 島 久登, 清治 和将, 高瀬 圭, 阿部 高明, 伊藤 貞嘉

    日本高血圧学会総会プログラム・抄録集　39回　390-390　2016/09

    Publisher: (NPO)日本高血圧学会

  93. 腎動脈狭窄による腎虚血診断のためのDiffusion-weighted MRIの有用性と臨床応用性の検討

    三島 英換, 大田 英揮, 鈴木 健弘, 菊地 晃一, 島 久登, 橋本 潤一郎, 高瀬 圭, 阿部 高明, 伊藤 貞嘉

    日本高血圧学会総会プログラム・抄録集　39回　358-358　2016/09

    Publisher: (NPO)日本高血圧学会

  94. Mitochonic Acid 5 Binds Mitochondria and Ameliorates Renal Tubular and Cardiac Myocyte Damage Peer-reviewed

    Takehiro Suzuki, Hiroaki Yamaguchi, Motoi Kikusato, Osamu Hashizume, Satoru Nagatoishi, Akihiro Matsuo, Takeya Sato, Tai Kudo, Tetsuro Matsuhashi, Kazutaka Murayanna, Yuki Ohba, Shun Watanabe, Shin-ichiro Kanno, Daichi Minaki, Daisuke Saigusa, Hiroko Shinbo, Nobuyoshi Mori, Akinori Yuri, Miyuki Yokoro, Eikan Mishima, Hisato Shima, Yasutoshi Akiyama, Yoichi Takeuchi, Koichi Kikuchi, Takafumi Toyohara, Chitose Suzuki, Takaharu Ichimura, Jun-ichi Anzai, Masahiro Kohzuki, Nariyasu Mario, Shigeo Kure, Teruyuki Yanagisawa, Yoshihisa Tomioka, Masaaki Toyomizu, Kohei Tsumoto, Kazuto Nakada, Joseph V. Bonventre, Sadayoshi Ito, Hitoshi Osaka, Ken-ichi Hayashi, Takaaki Abe

    JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY　27　(7)　1925-1932　2016/07

    DOI： 10.1681/ASN.2015060623 　

    ISSN： 1046-6673

    eISSN： 1533-3450

  95. SERIOUS HYPOCALCEMIA AFTER WITHDRAWAL OF VITAMIN D ANALOG IN BEDRIDDEN NONAGENARIANS WITH PREVIOUS THYROIDECTOMY: A REPORT OF TWO CASES Peer-reviewed

    Eikan Mishima, Kensuke Nishimiya, Yasushi Fujiwara, Masafumi Nishizawa, Hideyasu Kiyomoto, Sadayoshi Ito

    JOURNAL OF THE AMERICAN GERIATRICS SOCIETY　64　(6)　1374-1376　2016/06

    DOI： 10.1111/jgs.14171 　

    ISSN： 0002-8614

    eISSN： 1532-5415

  96. 一般住民における血中1-メチルアデノシン濃度と予後との関連性 大迫研究

    三島 英換, 菊地 晃一, 島 久登, 鈴木 健弘, 今井 潤, 伊藤 貞嘉, 阿部 高明

    日本腎臓学会誌　58　(3)　290-290　2016/05

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  97. ミトコンドリア病の新規治療薬Michonic acid-5(MA-5)はミトコンドリア機能不全と腎機能不全を改善する

    鈴木 健弘, 松橋 徹郎, 菊地 晃一, 島 久登, 竹内 陽一, 三島 英換, 秋山 泰利, 鈴木 千登世, 伊藤 貞嘉, 阿部 高明

    日本腎臓学会誌　58　(3)　277-277　2016/05

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  98. 抗TNF-α作用と抗TGF-β1作用を有する化合物の発見と臨床応用

    島 久登, 鈴木 健弘, 菊地 晃一, 三島 英換, 秋山 泰利, 鈴木 千登世, 伊藤 貞嘉, 阿部 高明

    日本腎臓学会誌　58　(3)　365-365　2016/05

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  99. Detection of Segmental Renal Ischemia by Diffusion-Weighted Magnetic Resonance Imaging: Clinical Utility for Diagnosis of Renovascular Hypertension Peer-reviewed

    Eikan Mishima, Koichi Kikuchi, Hideki Ota, Yasutoshi Akiyama, Takehiro Suzuki, Kazumasa Seiji, Junichiro Hashimoto, Kei Takase, Takaaki Abe, Sadayoshi Ito

    JOURNAL OF CLINICAL HYPERTENSION　18　(4)　364-365　2016/04

    DOI： 10.1111/jch.12675 　

    ISSN： 1524-6175

    eISSN： 1751-7176

  100. Impact of Small Renal Ischemia in Hypertension Development: Renovascular Hypertension Caused by Small Branch Artery Stenosis Peer-reviewed

    Eikan Mishima, Junichiro Hashimoto, Yasutoshi Akiyama, Hisato Shima, Kazumasa Seiji, Kei Takase, Takaaki Abe, Sadayoshi Ito

    JOURNAL OF CLINICAL HYPERTENSION　18　(3)　248-249　2016/03

    DOI： 10.1111/jch.12661 　

    ISSN： 1524-6175

    eISSN： 1751-7176

  101. Periodontitis-associated septic pulmonary embolism caused by Actinomyces species identified by anaerobic culture of bronchoalveolar lavage fluid: a case report Peer-reviewed

    Shun Endo, Eikan Mishima, Yoichi Takeuchi, Takashi Ohi, Masatsugu Ishida, Masaru Yanai, Hideyasu Kiyomoto, Tasuku Nagasawa, Sadayoshi Ito

    BMC INFECTIOUS DISEASES　15　552　2015/12

    DOI： 10.1186/s12879-015-1286-0 　

    ISSN： 1471-2334

  102. Immuno-Northern Blotting: Detection of RNA Modifications by Using Antibodies against Modified Nucleosides Peer-reviewed

    Eikan Mishima, Daisuke Jinno, Yasutoshi Akiyama, Kunihiko Itoh, Shinnosuke Nankumo, Hisato Shima, Koichi Kikuchi, Yoichi Takeuchi, Alaa Elkordy, Takehiro Suzuki, Kuniyasu Niizuma, Sadayoshi Ito, Yoshihisa Tomioka, Takaaki Abe

    PLOS ONE　10　(11)　e0143756　2015/11

    DOI： 10.1371/journal.pone.0143756 　

    ISSN： 1932-6203

  103. 粥状硬化性腎動脈狭窄症に対するステント治療の有効性と予後因子

    鈴木 健弘, 藤原 昌彦, 秋山 泰利, 三島 英換, 竹内 陽一, 鈴木 千登世, 横井 良明, 阿部 高明, 伊藤 貞嘉

    日本高血圧学会総会プログラム・抄録集　38回　358-358　2015/10

    Publisher: (NPO)日本高血圧学会

  104. PTRA時の末梢塞栓により治療後に高血圧が残存した線維筋性異形成による腎血管性高血圧の一例

    向山 靖乃, 三島 英換, 秋山 泰利, 菊地 晃一, 鈴木 健弘, 橋本 潤一郎, 阿部 高明, 伊藤 貞嘉

    日本腎臓学会誌　57　(6)　998-998　2015/08

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  105. Alteration of the Intestinal Environment by Lubiprostone Is Associated with Amelioration of Adenine-Induced CKD Peer-reviewed

    Eikan Mishima, Shinji Fukuda, Hisato Shinna, Akiyoshi Hirayama, Yasutoshi Akiyama, Yoichi Takeuchi, Noriko N. Fukuda, Takehiro Suzuki, Chitose Suzuki, Akinori Yuri, Koichi Kikuchi, Yoshihisa Tomioka, Sadayoshi Ito, Tomoyoshi Soga, Takaaki Abe

    JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY　26　(8)　1787-1794　2015/08

    DOI： 10.1681/ASN.2014060530 　

    ISSN： 1046-6673

    eISSN： 1533-3450

  106. Posterior reversible encephalopathy syndrome treated with renin-angiotensin system blockade Peer-reviewed

    Eikan Mishima, Junichiro Hashimoto, Yasutoshi Akiyama, Kazumasa Seiji, Kei Takase, Takaaki Abe, Sadayoshi Ito

    JOURNAL OF THE NEUROLOGICAL SCIENCES　355　(1-2)　219-221　2015/08

    DOI： 10.1016/j.jns.2015.06.007 　

    ISSN： 0022-510X

    eISSN： 1878-5883

  107. Mitochonic Acid 5 (MA-5), a Derivative of the Plant Hormone Indole-3-Acetic Acid, Improves Survival of Fibroblasts from Patients with Mitochondrial Diseases Peer-reviewed

    Takehiro Suzuki, Hiroaki Yamaguchi, Motoi Kikusato, Tetsuro Matsuhashi, Akihiro Matsuo, Takeya Sato, Yuki Oba, Shun Watanabe, Daichi Minaki, Daisuke Saigusa, Hiroko Shimbo, Nobuyoshi Mori, Eikan Mishima, Hisato Shima, Yasutoshi Akiyama, Yoichi Takeuchi, Akinori Yuri, Koichi Kikuchi, Takafumi Toyohara, Chitose Suzuki, Masahiro Kohzuki, Jun-ichi Anzai, Nariyasu Mano, Shigeo Kure, Teruyuki Yanagisawa, Yoshihisa Tomioka, Masaaki Toyomizu, Sadayoshi Ito, Hitoshi Osaka, Ken-ichiro Hayashi, Takaaki Abe

    TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE　236　(3)　225-232　2015/07

    DOI： 10.1620/tjem.236.225 　

    ISSN： 0040-8727

    eISSN： 1349-3329

  108. CE-MSによる透析患者に特異的な尿毒素の網羅的探索

    秋山 泰利, 菊地 晃一, 島 久登, 三島 英換, 中山 昌明, 伊藤 貞嘉, 曽我 朋義, 阿部 高明

    日本透析医学会雑誌　48　(Suppl.1)　753-753　2015/05

    Publisher: (一社)日本透析医学会

    ISSN： 1340-3451

    eISSN： 1883-082X

  109. 両側腎動脈狭窄を合併する悪性高血圧の治療におけるACE阻害薬の必要性

    三島 英換, 菊地 晃一, 秋山 泰利, 島 久登, 橋本 潤一郎, 阿部 高明, 伊藤 貞嘉

    日本高血圧学会臨床高血圧フォーラムプログラム・抄録集　4回　149-149　2015/05

    Publisher: (NPO)日本高血圧学会

  110. ベラプロストは腎不全時腎機能改善と尿毒症物質減少をもたらす

    大庭 悠貴, 松山 由香, 鈴木 康介, 宇留野 晃, 秋山 泰利, 三島 英換, 島 久登, 菊地 晃一, 伊藤 貞嘉, 阿部 高明

    日本腎臓学会誌　57　(3)　487-487　2015/04

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  111. GDF-15は急性腎障害およびCKDの腎機能障害の早期診断マーカー

    佐々木 駿, 小原 万妃, 櫻田 冴響, 秋山 泰利, 三島 英換, 島 久登, 菊地 晃一, 伊藤 貞嘉, 阿部 高明

    日本腎臓学会誌　57　(3)　540-540　2015/04

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  112. 抗炎症作用と抗線維化作用を有する化合物の探索と臨床応用

    島 久登, 菊地 晃一, 松橋 徹郎, 三島 英換, 秋山 泰利, 鈴木 健弘, 鈴木 千登世, 伊藤 貞嘉, 阿部 高明

    日本腎臓学会誌　57　(3)　569-569　2015/04

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  113. Exonic Mutations in the SLC12A3 Gene Cause Exon Skipping and Premature Termination in Gitelman Syndrome Peer-reviewed

    Yoichi Takeuchi, Eikan Mishima, Hisato Shima, Yasutoshi Akiyama, Chitose Suzuki, Takehiro Suzuki, Takayasu Kobayashi, Yoichi Suzuki, Tomohiro Nakayama, Yasuhiro Takeshima, Norma Vazquez, Sadayoshi Ito, Gerardo Gamba, Takaaki Abe

    JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY　26　(2)　271-279　2015/02

    DOI： 10.1681/ASN.2013091013 　

    ISSN： 1046-6673

    eISSN： 1533-3450

  114. ギテルマン症候群の新たな発症メカニズムとしてのエクソンスキッピングの発見

    竹内 陽一, 島 久登, 三島 英換, 秋山 泰利, 鈴木 千登世, 伊藤 貞嘉, 阿部 高明

    日本高血圧学会総会プログラム・抄録集　37回　328-328　2014/10

    Publisher: (NPO)日本高血圧学会

  115. Conformational Change in Transfer RNA Is an Early Indicator of Acute Cellular Damage Peer-reviewed

    Eikan Mishima, Chisako Inoue, Daisuke Saigusa, Ryusuke Inoue, Koki Ito, Yusuke Suzuki, Daisuke Jinno, Yuri Tsukui, Yosuke Akamatsu, Masatake Araki, Kimi Araki, Ritsuko Shimizu, Haruka Shinke, Takehiro Suzuki, Yoichi Takeuchi, Hisato Shima, Yasutoshi Akiyama, Takafumi Toyohara, Chitose Suzuki, Yoshikatu Saiki, Teiji Tominaga, Shigehito Miyagi, Naoki Kawagisihi, Tomoyoshi Soga, Takayoshi Ohkubo, Kenichi Yamamura, Yutaka Imai, Satohiro Masuda, Venkata Sabbisetti, Takaharu Ichimura, David B. Mount, Joseph V. Bonventre, Sadayoshi Ito, Yoshihisa Tomioka, Kunihiko Itoh, Takaaki Abe

    JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY　25　(10)　2316-2326　2014/10

    DOI： 10.1681/ASN.2013091001 　

    ISSN： 1046-6673

    eISSN： 1533-3450

  116. [111th Scientific Meeting of the Japanese Society of Internal Medicine: Symposium: 2. Perspective of treatment in the vascular lesion of various organs; 5) Biological aspect of chronic kidney disease and the new therapy]. Peer-reviewed

    Abe T, Mishima E, Itoh K, Hayashi K

    Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine　103　(9)　2158-2162　2014/09

    ISSN： 0021-5384

  117. 虚血ストレスに対するインドール・インドキシル化合物の保護効果の検討

    渡邉 駿, 大庭 悠貴, 松尾 明大, 島 久登, 竹内 陽一, 三島 英換, 秋山 泰利, 鈴木 千登世, 鈴木 健弘, 伊藤 貞嘉, 阿部 高明

    日本腎臓学会誌　56　(3)　322-322　2014/05

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  118. ミトコンドリア腎症患者培養線維芽細胞を用いたミトコンドリア機能改善薬物の探索

    松尾 明大, 大庭 悠貴, 渡邉 駿, 島 久登, 竹内 陽一, 三島 英換, 秋山 泰利, 鈴木 千登世, 鈴木 健弘, 伊藤 貞嘉, 阿部 高明

    日本腎臓学会誌　56　(3)　325-325　2014/05

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  119. 腎線維化、炎症改善効果を有する化合物の探索と臨床応用

    島 久登, 鈴木 健弘, 竹内 陽一, 三島 英換, 秋山 泰利, 鈴木 千登世, 伊藤 貞嘉, 阿部 高明

    日本腎臓学会誌　56　(3)　345-345　2014/05

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  120. エリスロポエチン産生増強化合物の作用機序の解明

    大庭 悠貴, 渡邉 駿, 松尾 明大, 島 久登, 竹内 陽一, 三島 英換, 秋山 泰利, 鈴木 千登世, 鈴木 健弘, 伊藤 貞嘉, 阿部 高明

    日本腎臓学会誌　56　(3)　398-398　2014/05

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  121. 抗1-methyladenosine抗体反応性分子の同定を目的としたtRNA分子種の解析法に関する研究

    津久井 佑梨, 陣野 大輔, 三島 英換, 鈴木 直人, 塚本 宏樹, 三枝 大輔, 伊藤 邦彦, 阿部 高明, 富岡 佳久

    日本薬学会年会要旨集　134年会　(2)　275-275　2014/03

    Publisher: (公社)日本薬学会

    ISSN： 0918-9823

  122. Indoxyl Sulfate Down-Regulates SLCO4C1 Transporter through Up-Regulation of GATA3 Peer-reviewed

    Yasutoshi Akiyama, Koichi Kikuchi, Daisuke Saigusa, Takehiro Suzuki, Yoichi Takeuchi, Eikan Mishima, Yasuaki Yamamoto, Ayako Ishida, Daiki Sugawara, Daisuke Jinno, Hisato Shima, Takafumi Toyohara, Chitose Suzuki, Tomokazu Souma, Takashi Moriguchi, Yoshihisa Tomioka, Sadayoshi Ito, Takaaki Abe

    PLOS ONE　8　(7)　2013/07

    DOI： 10.1371/journal.pone.0066518 　

    ISSN： 1932-6203

  123. Mutation of the Mg2+ transporter SLC41A1 results in a nephronophthisis-like phenotype Peer-reviewed

    Toby W. Hurd, Edgar A. Otto, Eikan Mishima, Heon Yung Gee, Hana Inoue, Masato Inazu, Hideomi Yamada, Jan Halbritter, George Seki, Masato Konishi, Weibin Zhou, Tsutomo Yamane, Satoshi Murakami, Gianluca Caridi, Gianmarco Ghiggeri, Takaaki Abe, Friedhelm Hildebrandt

    Journal of the American Society of Nephrology　24　(6)　967-977　2013/05/31

    DOI： 10.1681/ASN.2012101034 　

    ISSN： 1046-6673 1533-3450

  124. CE-MSを用いた透析患者の病態に特異的な尿毒症物質の同定

    秋山 泰利, 竹内 陽一, 三島 英換, 鈴木 健弘, 曽我 朋義, 伊藤 貞嘉, 阿部 高明

    日本腎臓学会誌　55　(3)　432-432　2013/04

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  125. tRNAの挙動検知はDNAダメージよりも早期の虚血組織障害マーカーとなる

    三島 英換, 井上 稚沙子, 三枝 大輔, 竹内 陽一, 秋山 泰利, 鈴木 健弘, 富岡 久佳, 伊藤 邦彦, 伊藤 貞嘉, 阿部 高明

    日本腎臓学会誌　55　(3)　296-296　2013/04

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  126. エリスロポエチン産生を増強させる化合物群の探索と同定(その2)

    鈴木 雄介, 佐原 利人, 池之内 初, 小原 万天, 鈴木 健弘, 鈴木 千登勢, 三島 英換, 竹内 陽一, 三枝 大輔, 富岡 佳久, 伊藤 貞嘉, 林 謙一郎, 阿部 高明

    日本腎臓学会誌　55　(3)　345-345　2013/04

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  127. A Metabolomic Approach to Clarifying the Effect of AST-120 on 5/6 Nephrectomized Rats by Capillary Electrophoresis with Mass Spectrometry (CE-MS) Peer-reviewed

    Yasutoshi Akiyama, Yoichi Takeuchi, Koichi Kikuchi, Eikan Mishima, Yasuaki Yamamoto, Chitose Suzuki, Takafumi Toyohara, Takehiro Suzuki, Atsushi Hozawa, Sadayoshi Ito, Tomoyoshi Soga, Takaaki Abe

    TOXINS　4　(11)　1309-1322　2012/11

    DOI： 10.3390/toxins4111309 　

    ISSN： 2072-6651

  128. アンジオテンシンType1受容体ブロッカーは慢性腎臓病患者においてeGERと相関せずにメチルグリオキサールを減少させる

    鈴木 健弘, 秋山 泰利, 竹内 陽一, 三島 英換, 伊藤 貞嘉, 中村 司, 阿部 高明

    日本高血圧学会総会プログラム・抄録集　35回　455-455　2012/09

    Publisher: (NPO)日本高血圧学会

  129. アンジオテンシンtype1受容体ブロッカーとチアゾリジンは尿毒素排泄トランスポーターの発現を制御する

    鈴木 健弘, 秋山 泰利, 竹内 陽一, 三島 英換, 伊藤 貞嘉, 阿部 高明

    日本高血圧学会総会プログラム・抄録集　35回　459-459　2012/09

    Publisher: (NPO)日本高血圧学会

  130. 慢性腎臓病患者のスタチンによる腎保護効果の検討

    青木 靖子, 鈴木 健弘, 秋山 泰利, 竹内 陽一, 三島 英換, 佐藤 博, 伊藤 貞嘉, 阿部 高明

    日本腎臓学会誌　54　(6)　718-718　2012/08

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  131. ARBは慢性腎臓病患者においてeGFRと相関せずメチルグリオキサールを減少させる

    池之内 初, 鈴木 健弘, 秋山 泰利, 竹内 陽一, 三島 英換, 伊藤 貞嘉, 中村 司, 阿部 高明

    日本腎臓学会誌　54　(6)　719-719　2012/08

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  132. 尿毒症物質によるエリスロポエチン産生低下の発症機序の解明

    秋山 泰利, 鈴木 健弘, 豊原 敬文, 竹内 陽一, 三島 英換, 佐藤 博, 伊藤 貞義, 阿部 高明

    日本内分泌学会雑誌　88　(1)　374-374　2012/04

    Publisher: (一社)日本内分泌学会

    ISSN： 0029-0661

    eISSN： 2186-506X

  133. ARBは慢性腎臓病患者においてeGFRと相関せずメチルグリオキサールを減少させる

    鈴木 健弘, 秋山 泰利, 竹内 陽一, 三島 英換, 伊藤 貞嘉, 中村 司, 阿部 高明

    日本腎臓学会誌　54　(3)　253-253　2012/04

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  134. ARBとチアゾリジンは尿毒素排泄トランスポーターの発現を制御する

    鈴木 健弘, 秋山 泰利, 竹内 陽一, 三島 英換, 伊藤 貞嘉, 阿部 高明

    日本腎臓学会誌　54　(3)　322-322　2012/04

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  135. SLCO4C1トランスポーター発現低下による尿毒症物質蓄積の悪循環の解明と新規治療法の開発

    秋山 泰利, 鈴木 健弘, 三島 英換, 竹内 陽一, 伊藤 貞嘉, 阿部 高明

    日本腎臓学会誌　54　(3)　322-322　2012/04

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  136. アンジオテンシンtype1受容体ブロッカーとチアゾリジンは尿毒素排泄トランスポーターの発現を制御する

    秋山 泰利, 鈴木 健弘, 竹内 陽一, 三島 英換, 伊藤 貞嘉, 阿部 高明

    日本高血圧学会臨床高血圧フォーラムプログラム・抄録集　1回　122-122　2012/04

    Publisher: (NPO)日本高血圧学会

  137. アンジオテンシンtype1受容体ブロッカーは慢性腎臓病患者においてeGFRと相関せずメチルグリオキサールを減少させる

    鈴木 健弘, 秋山 泰利, 竹内 陽一, 三島 英換, 伊藤 貞嘉, 中村 司, 阿部 高明

    日本高血圧学会臨床高血圧フォーラムプログラム・抄録集　1回　141-141　2012/04

    Publisher: (NPO)日本高血圧学会

  138. 尿毒症物質による尿毒症物質排泄トランスポーターSLCO4C1の転写制御と排泄促進の意義

    鈴木 健弘, 豊原 敬文, 秋山 泰利, 竹内 陽一, 三島 英換, 佐藤 博, 伊藤 貞嘉, 曽我 朋義, 阿部 高明

    日本高血圧学会総会プログラム・抄録集　34回　422-422　2011/10

    Publisher: (NPO)日本高血圧学会

  139. Metabolomic profiling of the autosomal dominant polycystic kidney disease rat model Peer-reviewed

    Takafumi Toyohara, Takehiro Suzuki, Yasutoshi Akiyama, Daisuke Yoshihara, Yoichi Takeuchi, Eikan Mishima, Koichi Kikuchi, Chitose Suzuki, Masayuki Tanemoto, Sadayoshi Ito, Shizuko Nagao, Tomoyoshi Soga, Takaaki Abe

    CLINICAL AND EXPERIMENTAL NEPHROLOGY　15　(5)　676-687　2011/10

    DOI： 10.1007/s10157-011-0467-4 　

    ISSN： 1342-1751

    eISSN： 1437-7799

  140. Transcriptional Regulation of Organic Anion Transporting Polypeptide SLCO4C1 as a New Therapeutic Modality to Prevent Chronic Kidney Disease Peer-reviewed

    Takehiro Suzuki, Takafumi Toyohara, Yasutoshi Akiyama, Yoichi Takeuchi, Eikan Mishima, Chitose Suzuki, Sadayoshi Ito, Tomoyoshi Soga, Takaaki Abe

    JOURNAL OF PHARMACEUTICAL SCIENCES　100　(9)　3696-3707　2011/09

    DOI： 10.1002/jps.22641 　

    ISSN： 0022-3549

  141. 尿細管ヘンレ上行脚Na+輸送を制御する新たな機構の解明

    三島 英換, 竹内 陽一, 秋山 泰利, 鈴木 健弘, 阿部 高明, 種本 雅之, 内田 俊也, 伊藤 貞嘉

    日本腎臓学会誌　53　(3)　367-367　2011/05

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  142. 尿毒症物質による尿毒症物質排泄トランスポーターSLCO4C1の転写制御の意義

    鈴木 健弘, 豊原 敬文, 秋山 泰利, 竹内 陽一, 三島 英換, 鈴木 千登世, 山口 浩明, 曽我 朋義, 伊藤 貞嘉, 阿部 高明

    日本腎臓学会誌　53　(3)　385-385　2011/05

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  143. クレメジン投与により低下する尿毒症物質の網羅的探索

    竹内 陽一, 三島 英換, 秋山 泰利, 鈴木 健弘, 鈴木 千登世, 曽我 朋義, 伊藤 貞嘉, 阿部 高明

    日本腎臓学会誌　53　(3)　432-432　2011/05

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  144. スタチンによる尿毒書物質排泄トランスポーターの発現制御と腎不全治療

    鈴木 健弘, 豊原 敬文, 秋山 泰利, 竹内 陽一, 三島 英換, 佐藤 博, 伊藤 貞嘉, 曽我 朋義, 阿部 高明

    日本内分泌学会雑誌　87　(1)　287-287　2011/04

    Publisher: (一社)日本内分泌学会

    ISSN： 0029-0661

    eISSN： 2186-506X

  145. Impact of the Oral Adsorbent AST-120 on Organ-Specific Accumulation of Uremic Toxins: LC-MS/MS and MS Imaging Techniques Peer-reviewed

    Sato E, Saigusa D, Mishima E, Uchida T, Miura D, Morikawa-Ichinose T, Kisu K, Sekimoto A, Saito R, Oe Y, Matsumoto Y, Tomioka Y, Mori T, Takahashi N, Sato H, Abe T, Niwa T, Ito S

    Toxins (Basel)　10　(1)　pii: E19　2011

  146. トランスポーター研究の臨床薬理 尿細管排泄機構と尿毒症物質 トランスポーター発現制御による腎不全治療

    鈴木 健弘, 豊原 敬文, 秋山 泰利, 竹内 陽一, 三島 英換, 中山 昌明, 佐藤 博, 伊藤 貞嘉, 曽我 朋義, 阿部 高明

    臨床薬理　41　(Suppl.)　S139-S139　2010/11

    Publisher: (一社)日本臨床薬理学会

    ISSN： 0388-1601

    eISSN： 1882-8272

  147. Stage of chronic kidney disease is an outcome-predicting factor of angioplasty for atheromatous renal artery stenosis Peer-reviewed

    Masayuki Tanemoto, Yoichi Takeuchi, Eikan Mishima, Takehiro Suzuki, Takaaki Abe, Sadayoshi Ito

    HYPERTENSION RESEARCH　33　(11)　1206-1210　2010/11

    DOI： 10.1038/hr.2010.152 　

    ISSN： 0916-9636

  148. トランスポーターを介したスタチンによる尿毒症性物質排泄強化による新たな慢性腎臓病治療

    豊原 敬文, 鈴木 健弘, 秋山 泰利, 竹内 陽一, 三島 英換, 種本 雅之, 中山 昌明, 伊藤 貞嘉, 曽我 朋義, 阿部 高明

    Diabetes Frontier　21　(5)　631-632　2010/10

    Publisher: (株)メディカルレビュー社

    ISSN： 0915-6593

  149. 尿毒症物質排泄を担う腎臓特異的有機アニオントランスポーターSLCO4C1のスタチンによる発現誘導効果の検討

    鈴木 健弘, 豊原 敬文, 秋山 泰利, 竹内 陽一, 三島 英換, 種本 雅之, 中山 昌明, 佐藤 博, 伊藤 貞嘉, 曽我 朋義, 阿部 高明

    日本高血圧学会総会プログラム・抄録集　33回　250-250　2010/10

    Publisher: (NPO)日本高血圧学会

  150. 動脈硬化性腎動脈狭窄を発見する為の予測因子の検討

    三島 英換, 齋藤 陽孝, 竹内 陽一, 秋山 泰利, 豊原 敬文, 鈴木 健弘, 種本 雅之, 阿部 高明, 伊藤 貞嘉

    日本高血圧学会総会プログラム・抄録集　33回　396-396　2010/10

    Publisher: (NPO)日本高血圧学会

  151. スタチンによる尿毒症物質排泄のメカニズムとその臨床応用

    豊原 敬文, 鈴木 健弘, 秋山 泰利, 竹内 陽一, 三島 英換, 種本 雅之, 中山 昌明, 佐藤 博, 伊藤 貞嘉, 曽我 朋義, 阿部 高明

    Therapeutic Research　31　(9)　1221-1223　2010/09

    Publisher: ライフサイエンス出版(株)

    ISSN： 0289-8020

  152. Metabolomic profiling of uremic solutes in CKD patients Peer-reviewed

    Takafumi Toyohara, Yasutoshi Akiyama, Takehiro Suzuki, Yoichi Takeuchi, Eikan Mishima, Masayuki Tanemoto, Ayako Momose, Naoko Toki, Hiroshi Sato, Masaaki Nakayama, Atsushi Hozawa, Ichiro Tsuji, Sadayoshi Ito, Tomoyoshi Soga, Takaaki Abe

    HYPERTENSION RESEARCH　33　(9)　944-952　2010/09

    DOI： 10.1038/hr.2010.113 　

    ISSN： 0916-9636

  153. Urinary stones resembling uric acid stones. International-journal Peer-reviewed

    Masayuki Tanemoto, Yoichi Takeuchi, Eikan Mishima, Takehiro Suzuki, Takaaki Abe, Sadayoshi Ito

    NDT plus　3　(3)　318-319　2010/06

    DOI： 10.1093/ndtplus/sfq008 　

  154. CKD患者と腎不全ラットにおける腎不全物質の網羅的解析

    豊原 敬文, 秋山 泰利, 鈴木 健弘, 竹内 陽一, 三島 英換, 種本 雅之, 佐藤 博, 中山 昌明, 伊藤 貞嘉, 曽我 朋義, 阿部 高明

    日本透析医学会雑誌　43　(Suppl.1)　363-363　2010/05

    Publisher: (一社)日本透析医学会

    ISSN： 1340-3451

    eISSN： 1883-082X

  155. CE-MSを用いた血液透析前後の尿毒症物質除去効率の網羅的解析

    秋山 泰利, 竹内 陽一, 三島 英換, 豊原 敬文, 鈴木 健弘, 種本 雅之, 中山 昌明, 伊藤 貞嘉, 曽我 朋義, 阿部 高明

    日本透析医学会雑誌　43　(Suppl.1)　800-800　2010/05

    Publisher: (一社)日本透析医学会

    ISSN： 1340-3451

    eISSN： 1883-082X

  156. 腎臓特異的有機アニオントランスポーターSLCO4C1による腎不全物質排泄促進を介した高血圧と腎内炎症の改善

    鈴木 健弘, 豊原 敬文, 秋山 泰利, 竹内 陽一, 三島 英換, 種本 雅之, 中山 昌明, 伊藤 貞嘉, 曽我 朋義, 阿部 高明

    日本腎臓学会誌　52　(3)　281-281　2010/05

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  157. キャピラリー電気泳動質量分析により同定された新規ヒト腎不全物質18種類の毒性と酸化ストレス惹起

    菊地 晃一, 豊原 敬文, 秋山 泰利, 鈴木 健弘, 竹内 陽一, 三島 英換, 種本 雅之, 佐藤 博, 中山 昌明, 伊藤 貞嘉, 曽我 朋義, 阿部 高明

    日本腎臓学会誌　52　(3)　281-281　2010/05

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  158. CE-MSを用いた血液透析前後の尿毒症物質除去効率の網羅的解析

    秋山 泰利, 竹内 陽一, 三島 英換, 豊原 敬文, 鈴木 健弘, 種本 雅之, 中山 昌明, 伊藤 貞嘉, 曽我 朋義, 阿部 高明

    日本腎臓学会誌　52　(3)　378-378　2010/05

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  159. UREMIC TOXIN TRANSPORTER SLCO4C1 IS ENHANCED BY STATINS

    Suzuki Takehiro, Toyohara Takahumi, Akiyama Yasutoshi, Takuuchi Yoichi, Mishima Eikan, Tanemoto Masayuki, Ito Sadayoshi, Soga Tomoyoshi, Abe Takaaki

    Abstracts of Annual meeting of Japanese Society for the Study of Xenobiotics　25　44-44　2010

    Publisher: The Japanese Society for the Study of Xenobiotics

    DOI： 10.14896/jssxmeeting.25.0.44.0 　

  160. The HMG-CoA Reductase Inhibitor Pravastatin Stimulates Insulin Secretion through Organic Anion Transporter Polypeptides Peer-reviewed

    Michiaki Abe, Takafumi Toyohara, Akiko Ishii, Takehiro Suzuki, Naoya Noguchi, Yasutoshi Akiyama, Hiromi O. Shiwaku, Rie Nakagomi-Hagihara, Guodong Zheng, Eisuke Shibata, Tomokazu Souma, Tomohiko Shindo, Hirohito Shima, Yoichi Takeuchi, Eikan Mishima, Masayuki Tanemoto, Tetsuya Terasaki, Tohru Onogawa, Michiaki Unno, Sadayoshi Ito, Shin Takasawa, Takaaki Abe

    DRUG METABOLISM AND PHARMACOKINETICS　25　(3)　274-282　2010

    DOI： 10.2133/dmpk.25.274 　

    ISSN： 1347-4367

  161. SLCO4C1 Transporter Eliminates Uremic Toxins and Attenuates Hypertension and Renal Inflammation Peer-reviewed

    Takafumi Toyohara, Takehiro Suzuki, Ryo Morimoto, Yasutoshi Akiyama, Tomokazu Souma, Hiromi O. Shiwaku, Yoichi Takeuchi, Eikan Mishima, Michiaki Abe, Masayuki Tanemoto, Satohiro Masuda, Hiroaki Kawano, Koji Maernura, Masaaki Nakayama, Hiroshi Sato, Tsuyoshi Mikkaichi, Hiroaki Yamaguchi, Shigefumi Fukui, Yoshihiro Fukumoto, Hiroaki Shimokawa, Ken-ichi Inui, Tetsuya Terasaki, Junichi Goto, Sadayoshi Ito, Takanori Hishinuma, Isabelle Rubera, Michel Tauc, Yoshiaki Fujii-Kuriyama, Hikaru Yabuuchi, Yoshinori Moriyama, Tomoyoshi Soga, Takaaki Abe

    JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY　20　(12)　2546-2555　2009/12

    DOI： 10.1681/ASN.2009070696 　

    ISSN： 1046-6673

    eISSN： 1533-3450

  162. Manipulate expression of the kidney specific organic anion transporter SLCO4C1

    Toyohara Takafumi, Suzuki Takehiro, Akiyama Yasutoshi, Takeuchi Yoichi, Mishima Eikan, Abe Michiaki, Tanemoto Masayuki, Ito Sadayoshi, Abe Takaaki

    Abstracts of Annual meeting of Japanese Society for the Study of Xenobiotics　24　56-56　2009

    Publisher: The Japanese Society for the Study of Xenobiotics

    DOI： 10.14896/jssxmeeting.24.0.56.0 　

Show all ︎Show first 5

Misc. 78

  1. Exhalation omics based on sulfur metabolites in chronic kidney disease

    逸見佳宣, 緒方星陵, 高田剛, 三枝大輔, 三島英換, WEI Fanyan, 赤池孝章, 高橋信行, 佐藤恵美子

    衛生薬学・環境トキシコロジー講演要旨集　2024　2024

    ISSN： 0919-2115

  2. Effects of low birthweight on blood pressure, renal development, and the next generation and study of their treatment

    佐藤恵美子, 佐藤恵美子, 堰本晃代, 山越聖子, 伏木由衣, 三枝大輔, 高橋信行, 高橋信行, 三島英換

    日本高血圧学会総会プログラム・抄録集(CD-ROM)　46th　2024

  3. CaSR刺激型自己抗体による副甲状腺機能低下症の合併が疑われた腎血管性高血圧の1例

    上原啓誠, 豊原敬文, 三島英換, 渡邉駿, 菊地晃一, 鈴木健弘, 伊東伸朗, 宮崎真理子, 阿部高明

    日本腎臓学会誌(Web)　63　(6-E)　2021

    ISSN： 1884-0728

  4. まれな変異に重点を置いた尿酸値の遺伝率の研究

    三澤計治, 三澤計治, 三澤計治, 三澤計治, 三島英換, 長谷川嵩矩, 大内基司, 小島要, 河合洋介, 松尾雅文, 安西尚彦, 長崎正朗

    日本人類遺伝学会大会プログラム・抄録集　66th (CD-ROM)　2021

  5. Quantitative analysis of gut microbiota-derived metabolites by LC-MS sheds light on the gut-kidney axis on kidney disease

    金光祥臣, 三島英換, 松本洋太郎, 前川正充, 前川正充, 菊地晃一, 三枝大輔, 阿部高明, 阿部高明, 眞野成康, 眞野成康, 富岡佳久

    JSBMS Letters　46　(Supplement)　2021

    ISSN： 1881-5464

  6. Effects of the oral adsorbent AST-120 on fecal p-cresol and indole levels and on the gut microbiota composition. International-journal

    Emiko Sato, Koji Hosomi, Akiyo Sekimoto, Eikan Mishima, Yuji Oe, Daisuke Saigusa, Sadayoshi Ito, Takaaki Abe, Hiroshi Sato, Jun Kunisawa, Toshimitsu Niwa, Nobuyuki Takahashi

    Biochemical and biophysical research communications　525　(3)　773-779　2020/05/07

    DOI： 10.1016/j.bbrc.2020.02.141 　

    More details Close

    In chronic kidney disease, elevated levels of circulating uremic toxins are associated with a variety of symptoms and organ dysfunction. Indoxyl sulfate (IS) and p-cresyl sulfate (pCS) are microbiota-derived metabolites and representative uremic toxins. We have previously shown that the oral adsorbent AST-120 profoundly reduced pCS compared to IS in adenine-induced renal failure in mice. However, the mechanisms of the different attenuation effects of AST-120 between IS and pCS are unclear. To clarify the difference of AST-120 on IS and pCS, we investigated the levels of fecal indole and p-cresol, the respective precursors of IS and pCS, and examined the influence on the gut microbiota. Although fecal indole was detected in all groups analyzed, fecal p-cresol was not detected in AST-120 treatment groups. In genus level, a total of 23 organisms were significantly changed by renal failure or AST-120 treatment. Especially, AST-120 reduced the abundance of Erysipelotrichaceae uncultured and Clostridium sensu stricto 1, which have a gene involved in p-cresol production. Our findings suggest that, in addition to the adsorption of the uremic toxin precursors, AST-120 affects the abundance of some gut microbiota in normal and renal failure conditions, thereby explaining the different attenuation effects on IS and pCS.

  7. Uric acid elevation by favipiravir, an antiviral drug

    Eikan Mishima, Naohiko Anzai, Mariko Miyazaki, Takaaki Abe

    Tohoku Journal of Experimental Medicine　251　(2)　87-90　2020

    Publisher: Tohoku University Medical Press

    DOI： 10.1620/tjem.251.87 　

    ISSN： 1349-3329 0040-8727

  8. 糖尿病性腎症の発症・進展予測マーカーとしてのフェニル硫酸の有用性

    菊地晃一, 三枝大輔, 金光祥臣, 松本洋太郎, 三瀬広記, 中村智洋, 三島英換, 豊原敬文, 鈴木健弘, 寳澤篤, 和田淳, 富岡佳久, 阿部高明

    日本腎臓学会誌(Web)　62　(4)　2020

    ISSN： 1884-0728

  9. アデニン誘発腎不全マウスにおけるエロビキシバットの効果

    秋山由雅子, 前川正充, 金光祥臣, 菊地晃一, 何欣蓉, 三島英換, 鈴木健弘, 一條真梨子, 鈴木千登世, 眞野成康, 富岡佳久, 阿部高明

    日本腎臓学会誌(Web)　62　(4)　2020

    ISSN： 1884-0728

  10. 胆汁酸トランスポーター阻害薬エロビキシバットによる腎保護作用の検討

    秋山由雅子, 何欣蓉, 金光祥臣, 前川正充, 菊地晃一, 鈴木健弘, 三島英換, 一條真梨子, 鈴木千登世, 眞野成康, 富岡佳久, 伊藤貞嘉, 阿部高明

    日本腎臓学会誌　61　(3)　403-403　2019/05/15

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  11. 腸内細菌由来のフェニル硫酸は糖尿病性腎臓病でのアルブミン尿増悪の原因物質かつ予測マーカーである

    菊地晃一, 三枝大輔, 金光祥臣, 松本洋太郎, 中村智洋, 淺地圭, 三瀬広記, 何欣蓉, 三島英換, 鈴木健弘, 和田淳, 寶澤篤, 伊藤貞嘉, 阿部高明

    日本腎臓学会誌　61　(3)　312-312　2019/05/15

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  12. 既存薬スクリーニングによる抗フェロトーシス薬の同定と急性腎障害保護効果の検討

    三島英換, 佐藤恵美子, 鈴木健弘, 伊藤貞嘉, 阿部高明

    日本腎臓学会誌　61　(3)　2019

    ISSN： 0385-2385

  13. 腸腎連関に基づく慢性腎臓病の病態解明と新規治療法の開発

    三島 英換

    東北医学雑誌　130　(1)　57-59　2018/06

    Publisher: 東北医学会

    ISSN： 0040-8700

  14. 【腎と透析ベッドサイド検査事典】 (第2章)生化学検査(一般) 低・中分子生化学物質 パラクレシル硫酸

    三島 英換, 阿部 高明

    腎と透析　84　(増刊)　57-58　2018/05

    Publisher: (株)東京医学社

    ISSN： 0385-2156

  15. グアニル酸シクラーゼC受容体作動薬リナクロチドは腎不全に伴う腸内環境悪性化を改善し腎線維化を抑制する

    南都文香, 福田真嗣, 金光祥臣, 三枝大輔, 菊地晃一, 何欣蓉, 三島英換, 鈴木健弘, 松橋徹郎, 及川義嗣, 鈴木千登世, 富岡佳久, 曽我朋義, 伊藤貞嘉, 阿部高明

    日本腎臓学会誌　60　(3)　463-463　2018/04/30

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

  16. 【腎疾患診療の未来 最新知見のエッセンシャル】 腎臓基礎研究の最先端 腎不全患者の尿毒症毒素に対する治療

    三島 英換, 阿部 高明

    診断と治療　106　(4)　466-471　2018/04

    Publisher: (株)診断と治療社

    ISSN： 0370-999X

  17. 腎腸連関 腸内細菌叢が慢性腎臓病に与える正負両側面の影響

    三島 英換, 阿部 高明

    日本腎臓学会誌　60　(3)　299-299　2018/04

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

  18. 【高齢者の腎不全対策-透析を減らすために】 Key words 腎臓病とゲノム医療

    三島 英換, 清元 秀泰

    カレントテラピー　36　(3)　290-290　2018/03

    Publisher: (株)ライフメディコム

    ISSN： 0287-8445

  19. レアバリアントが尿酸値の失われた遺伝率のかなりの割合を説明する

    三澤計治, 三澤計治, 三島英換, 大内基司, 長谷川嵩矩, 小島要, 小島要, 河合洋介, 長崎正朗, 長崎正朗, 安西尚彦, 安西尚彦, 阿部高明, 山本雅之, 山本雅之

    日本人類遺伝学会大会プログラム・抄録集　63rd　2018

  20. ミトコンドリア病新規治療薬MA‐5はATP合成酵素のダイマー化によりATP合成を促進させ細胞保護効果を発揮する

    松橋徹郎, 佐藤岳哉, 菅野新一郎, 鈴木健弘, 及川善嗣, 菊地晃一, 南都文香, 何欣蓉, 秋山由雅子, 鈴木千登世, 三島英換, 呉繁夫, 林謙一郎, 中田和人, 小坂仁, 阿部高明

    日本ミトコンドリア学会年会要旨集　17th　54　2017/11/06

  21. 【いま知りたい!腸内フローラのABC】 腸内フローラと疾患のかかわり 慢性腎臓病(CKD)

    三島 英換, 阿部 高明

    Medical Technology　45　(10)　1027-1031　2017/10

    Publisher: 医歯薬出版(株)

    ISSN： 0389-1887

  22. tRNAと細胞障害

    三島 英換

    循環器内科　82　(4)　370-374　2017/10

    Publisher: (有)科学評論社

    ISSN： 1884-2909

  23. LC-MS/MSとイメージングMSによる腎不全時における尿毒素臓器蓄積とAST-120による治療効果の評価

    佐藤 恵美子, 三枝 大輔, 三島 英換, 三浦 大典, 佐藤 博, 丹羽 利充, 伊藤 貞嘉

    JSBMS Letters　42　(Suppl.)　97-97　2017/08

    Publisher: (一社)日本医用マススペクトル学会

    ISSN： 1881-5464

  24. 【高血圧 高血圧学アップデート】 この症例から何を学ぶか 多血症と高度の蛋白尿を合併した腎血管性高血圧

    三島 英換, 阿部 高明

    Medical Practice　34　(8)　1372-1375　2017/08

    Publisher: (株)文光堂

    ISSN： 0910-1551

  25. 腸腎連関から導く腎臓病の病態解明と治療法の開発

    三島 英換, 阿部 高明

    BIO Clinica　32　(5)　506-511　2017/05

    Publisher: (株)北隆館

    ISSN： 0919-8237

  26. 【他臓器とのつながりで考える腎疾患治療】 見えてきた腸腎連関の存在

    三島 英換, 阿部 高明

    日本内科学会雑誌　106　(5)　919-925　2017/05

    Publisher: (一社)日本内科学会

    DOI： 10.2169/naika.106.919 　

    ISSN： 0021-5384

  27. 【腸内細菌叢と腎疾患】 腸内細菌叢が腎臓病に与える影響 正と負の両側面から

    三島 英換, 阿部 高明

    日本腎臓学会誌　59　(4)　557-561　2017/05

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

  28. 抗TNF‐α作用と抗TGF‐β1作用を有する新規抗線維化薬Mitochonic acid 35(MA‐35)の開発

    島久登, 佐々木健介, 鈴木健弘, 三島英換, 菊地晃一, 松橋徹郎, 及川善嗣, 秋山由雅子, 南都文香, 何欣蓉, 鈴木千登世, 正木崇生, 伊藤貞嘉, 阿部高明

    日本腎臓学会誌　59　(3)　258　2017/04/25

    ISSN： 0385-2385

  29. 腎動脈狭窄による腎虚血評価のための拡散強調MRIの有用性と臨床応用性

    三島英換, 大田英揮, 鈴木健弘, 秋山由雅子, 高瀬圭, 阿部高明, 伊藤貞嘉

    日本腎臓学会誌　59　(3)　232　2017/04/25

    ISSN： 0385-2385

  30. 腎不全時における全身臓器での尿毒素蓄積とAST-120による蓄積軽減効果

    佐藤 恵美子, 三島 英換, 三枝 大輔, 内田 多恵子, 高橋 信行, 佐藤 博, 丹羽 利充, 森 建文, 伊藤 貞嘉

    日本腎臓学会誌　59　(3)　283-283　2017/04

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  31. ミトコンドリア病新規治療薬Mitochonic Acid(MA)-5は腎障害を有するミトコンドリア病患者に対する新規治療薬となる

    松橋 徹郎, 鈴木 健弘, 及川 善嗣, 秋山 由雅子, 菊地 晃一, 島 久登, 三島 英換, 秋山 泰利, 鈴木 千登世, 呉 繁夫, 伊藤 貞嘉, 阿部 高明

    日本腎臓学会誌　59　(3)　236-236　2017/04

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  32. 尿毒素による細胞内代謝変化は慢性腎臓病においてサルコペニアを引き起こす

    佐藤 恵美子, 三島 英換, 森 建文, 鈴木 亜里沙, 三枝 大輔, 高橋 信行, 佐藤 博, 丹羽 利充, 阿部 高明, 伊藤 貞嘉

    日本薬学会年会要旨集　137年会　(4)　89-89　2017/03

    Publisher: (公社)日本薬学会

    ISSN： 0918-9823

  33. Indole analogs have novel therapeutic effects on mitochondrial diseases

    Tetsuro Matsuhashi, Takehiro Suzuki, Akihiro Matsuo, Yuuki Oba, Kousuke Suzuki, Kouichi Kikuchi, Hisato Shima, Youichi Takeuchi, Eikan Mishima, Yasutoshi Akiyama, Chitose Suzuki, Takeya Sato, Teruyuki Yanagisawa, Kenichiro Hayashi, Hitoshi Osaka, Kazuto Nakada, Takaaki Abe

    MITOCHONDRION　31　96-97　2016/11

    ISSN： 1567-7249

    eISSN： 1872-8278

  34. 用語解説 腸内細菌と腎臓病

    三島 英換, 阿部 高明

    腎・高血圧の最新治療　5　(4)　187-187　2016/10

    Publisher: (有)フジメディカル出版

    ISSN： 2187-0004

  35. 本邦の腎動脈病変を有する線維筋性異形成患者における頭頸部血管病変の合併頻度

    梅澤 周, 三島 英換, 鈴木 健弘, 菊地 晃一, 島 久登, 橋本 潤一郎, 阿部 高明, 伊藤 貞嘉

    日本高血圧学会総会プログラム・抄録集　39回　358-358　2016/09

    Publisher: (NPO)日本高血圧学会

  36. 高血圧緊急症の急性期病態における脳・眼底・腎臓の高血圧性臓器障害の相互連動性

    船山 由希乃, 三島 英換, 鈴木 健弘, 菊地 晃一, 島 久登, 橋本 潤一郎, 阿部 高明, 伊藤 貞嘉

    日本高血圧学会総会プログラム・抄録集　39回　323-323　2016/09

    Publisher: (NPO)日本高血圧学会

  37. CKDにおけるサルコペニアの発症機序の解明

    佐藤 恵美子, 森 建文, 三島 英換, 鈴木 亜里沙, 高橋 信行, 佐藤 博, 丹羽 利充, 阿部 高明, 伊藤 貞嘉

    日本高血圧学会総会プログラム・抄録集　39回　329-329　2016/09

    Publisher: (NPO)日本高血圧学会

  38. 筋細胞における尿毒素性酸化ストレスは代謝変化を引き起こしサルコペニアの原因となる

    佐藤恵美子, 佐藤恵美子, 森建文, 三島英換, 鈴木亜里沙, 庭野吉己, 高橋信行, 高橋信行, 佐藤博, 佐藤博, 丹羽利充, 阿部高明, 伊藤貞嘉

    日本酸化ストレス学会学術集会プログラム・抄録集　69th　126　2016/08/30

  39. 【誰も教えてくれなかった-慢性便秘の診かた】 ケース別対応 慢性腎臓病および透析患者の便秘

    三島 英換, 阿部 高明

    Medicina　53　(9)　1420-1423　2016/08

    Publisher: (株)医学書院

    ISSN： 0025-7699

  40. 【最近の腎臓・透析領域の新薬とその使い方のコツ】 ルビプロストン

    三島 英換, 阿部 高明

    腎と透析　81　(2)　243-245　2016/08

    Publisher: (株)東京医学社

    ISSN： 0385-2156

  41. インドキシル硫酸によるウレミックサルコペニア発症機序解明

    佐藤 恵美子, 森 建文, 三島 英換, 鈴木 亜里沙, 佐藤 博, 丹羽 利充, 阿部 高明, 伊藤 貞嘉

    日本腎臓学会誌　58　(3)　315-315　2016/05

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

  42. 腎臓のバイオマーカーと創薬戦略

    鈴木 健弘, 三島 英換, 三枝 大輔, 阿部 高明

    実験医学　34　(8)　1262-1269　2016/05

    Publisher: (株)羊土社

    ISSN： 0288-5514

  43. ミトコンドリア病の新規治療薬Michonic acid-5(MA-5)

    松橋 徹郎, 鈴木 健弘, 菊地 晃一, 島 久登, 三島 英換, 秋山 泰利, 小坂 仁, 呉 繁夫, 阿部 高明

    日本内科学会雑誌　105　(Suppl.)　183-183　2016/02

    Publisher: (一社)日本内科学会

    ISSN： 0021-5384

    eISSN： 1883-2083

  44. 【腎臓とアンチエイジング】 腸内細菌と慢性腎臓病

    三島 英換, 福田 真嗣, 阿部 高明

    アンチ・エイジング医学　12　(1)　018-023　2016/02

    Publisher: (株)メディカルレビュー社

    ISSN： 1880-1579

  45. ルビプロストンの腸内環境改善を介したアデニンCKDモデルにおける腎障害抑制効果

    三島英換, 福田真嗣, 秋山泰利, 島久登, 菊地晃一, 鈴木健弘, 伊藤貞嘉, 阿部高明

    日本腎臓学会誌　57　(3)　472-472　2015/04/30

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  46. 尿毒素蓄積における腸内細菌叢の関与―無菌腎不全マウスとCE‐TOFMSを用いた解析―

    三島英換, 福田真嗣, 秋山泰利, 島久登, 菊地晃一, 鈴木健弘, 伊藤貞嘉, 阿部高明

    日本腎臓学会誌　57　(3)　472-472　2015/04/30

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  47. LC/MS/MSによる修飾核酸一斉定量法の構築と応用

    陣野大輔, 齋藤一樹, 南雲信之介, 金光祥臣, 塚本宏樹, 松本洋太郎, 三島英換, 鈴木千登世, 阿部高明, 富岡佳久

    日本薬学会東北支部大会講演要旨集　54th　2015

  48. 5) Biological Aspect of Chronic Kidney Disease and the New Therapy

    Takaaki Abe, Eikan Mishima, Kunihiko Itoh, Ken-ichiro Hayashi

    Nihon Naika Gakkai Zasshi　103　(9)　2158-2162　2014/09

    Publisher: Japanese Society of Internal Medicine

    DOI： 10.2169/naika.103.2158 　

    ISSN： 0021-5384

  49. 【最新臨床高血圧学-高血圧治療の最前線-】 ライフステージ・タイプ別の高血圧の治療・管理 合併症を有する高血圧 CKD

    三島 英換, 伊藤 貞嘉

    日本臨床　72　(増刊6 最新臨床高血圧学)　454-458　2014/08

    Publisher: (株)日本臨床社

    ISSN： 0047-1852

  50. エクソンスキッピング ギテルマン症候群の新たな発症メカニズム

    竹内陽一, 島久登, 三島英換, 秋山泰利, 中山智祥, 竹島泰弘, GAMBA G, 伊藤貞嘉, 阿部高明

    日本腎臓学会誌　56　(3)　316-316　2014/05/25

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  51. メタゲノムとメタボローム解析による腎不全時の腸内環境変化の検討

    三島英換, 福田真嗣, 秋山泰利, 伊藤貞嘉, 曽我朋義, 阿部高明

    日本腎臓学会誌　56　(3)　256-256　2014/05/25

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  52. PPAR γ agonistによる大血管周術期腎障害予防効果の実験的検討

    伊藤 校輝, 川本 俊輔, 神田 桂輔, 鈴木 智之, 片平 晋太郎, 松尾 諭志, 早津 幸弘, 鈴木 佑輔, 三島 英換, 岡村 将史, 齋木 由利子, 本吉 直孝, 堀井 明, 阿部 高明, 齋木 佳克

    日本心臓血管外科学会雑誌　43　(Suppl.)　384-384　2014/01

    Publisher: (NPO)日本心臓血管外科学会

    ISSN： 0285-1474

    eISSN： 1883-4108

  53. 新規腎障害マーカーとしての1-メチルアデノシンの検討

    陣野大輔, 鈴木直人, 津久井佑梨, 三枝大輔, 三島英換, 鈴木千登世, 塚本宏樹, 阿部高明, 富岡佳久

    日本薬学会東北支部大会講演要旨集　52nd　2013

  54. 5-アミノレブリン酸は炎症時のEpo産生能低下を改善する

    一条 貞満, 秋山 泰利, 鈴木 健弘, 鈴木 千登勢, 古山 和道, 三島 英換, 竹内 陽一, 伊藤 貞嘉, 阿部 高明

    日本腎臓学会誌　54　(3)　320-320　2012/04

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  55. スタチンによる尿毒症物質排泄トランスポーター発現制御と腎不全治療 (Therapeutic Reserch )

    鈴木健弘, 豊原敬文, 秋山泰利, 竹内陽一, 三島英換, 佐藤博, 伊藤貞嘉, 曽我朋義, 阿部高明

    Therapeutic Reserch　33　201-203　2012/03

  56. 慢性腎臓病患者のスタチンによる腎保護効果の検討

    鈴木健弘, 秋山泰利, 竹内陽一, 三島英換, 三枝大輔, 佐藤博, 伊藤貞嘉, 阿部高明, 阿部高明, 阿部高明

    Therapeutic Research　33　(8)　2012

    ISSN： 0289-8020

  57. 【高血圧症の最前線】 細胞内呼吸と高血圧

    三島 英換, 阿部 高明

    細胞　44　(1)　8-11　2012/01

    Publisher: (株)ニュー・サイエンス社

    ISSN： 1346-7557

  58. 中心脈圧および大動脈スティフネスは腎血流動態を介してアルブミン尿と関連する 腎動脈ドップラ法を用いた検討

    橋本 潤一郎, 岩倉 芳倫, 小野 美澄, 三島 英換, 竹内 陽一, 森本 玲, 工藤 正孝, 鈴木 健弘, 阿部 倫明, 佐藤 文俊, 阿部 高明, 伊藤 貞嘉

    日本高血圧学会総会プログラム・抄録集　34回　460-460　2011/10

    Publisher: (NPO)日本高血圧学会

  59. CKDの治療のすすめかたとその実際 RAS阻害薬の適応と使いかた

    三島 英換, 伊藤 貞嘉

    Medical Practice　28　(6)　1073-1076　2011/06

    Publisher: (株)文光堂

    ISSN： 0910-1551

  60. 尿毒症物質はEpo受容体発現量を低下させEpo抵抗性を惹起する

    山本恭彰, 秋山泰利, 鈴木健弘, 竹内陽一, 三島英換, 鈴木千登世, 伊藤貞嘉, 曽我朋義, 小松則夫, 阿部高明

    日本腎臓学会誌　53　(3)　386-386　2011/05/25

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  61. 診療ガイドラインからみた血圧・血糖・脂質管理と薬物治療のトレンド 高血圧症

    三島 英換, 阿部 高明

    薬局　62　(5)　2410-2415　2011/04

    Publisher: (株)南山堂

    ISSN： 0044-0035

  62. 脈圧増幅、末梢圧波反射、および大動脈スティフネスが拍動性動脈血流に及ぼす影響

    橋本 潤一郎, 岩倉 芳倫, 三島 英換, 竹内 陽一, 森本 玲, 工藤 正孝, 阿部 倫明, 種本 雅之, 佐藤 文俊, 阿部 高明, 伊藤 貞嘉

    日本高血圧学会総会プログラム・抄録集　33回　276-276　2010/10

    Publisher: (NPO)日本高血圧学会

  63. Metabolomic profiling of uremic solutes in CKD patients (vol 33, pg 945, 2010)

    Takafumi Toyohara, Yasutoshi Akiyama, Takehiro Suzuki, Yoichi Takeuchi, Eikan Mishima, Masayuki Tanemoto, Ayako Momose, Naoko Toki, Hiroshi Sato, Masaaki Nakayama, Atsushi Hozawa, Ichiro Tsuji, Sadayoshi Ito, Tomoyoshi Soga, Takaaki Abe

    HYPERTENSION RESEARCH　33　(10)　1089-1089　2010/10

    DOI： 10.1038/hr.2010.158 　

    ISSN： 0916-9636

  64. CKD患者における尿毒症物質の解析

    秋山 泰利, 鈴木 健弘, 豊原 敬文, 竹内 陽一, 三島 英換, 種本 雅之, 中山 昌明, 佐藤 博, 寳澤 篤, 辻 一郎, 伊藤 貞嘉, 曽我 朋義, 阿部 高明

    日本高血圧学会総会プログラム・抄録集　33回　365-365　2010/10

    Publisher: (NPO)日本高血圧学会

  65. ADPKDモデルラットにおける腎不全物質の網羅的解析

    豊原 敬文, 秋山 泰利, 鈴木 健弘, 竹内 陽一, 三島 英換, 種本 雅之, 伊藤 貞嘉, 長尾 枝澄香, 曽我 朋義, 阿部 高明

    日本腎臓学会誌　52　(3)　396-396　2010/05

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  66. CKD患者の尿毒症物質と早期診断マーカーの網羅的解析

    豊原 敬文, 秋山 泰利, 鈴木 健弘, 竹内 陽一, 三島 英換, 種本 雅之, 佐藤 博, 中山 昌明, 寳澤 篤, 辻 一郎, 伊藤 貞嘉, 曽我 朋義, 阿部 高明

    日本腎臓学会誌　52　(3)　340-340　2010/05

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  67. 【内分泌クリニカル・カンファランス】 副腎 顕著なクッシング徴候を示さなかったコルチゾル産生副腎皮質癌の1例 (ホルモンと臨床)

    工藤正孝, 三島英換, 佐藤和則, 森本玲, 佐藤文俊, 村上治, 三井一浩, 坂本和宏, 太田耕造, 笹野公伸, 伊藤貞嘉

    ホルモンと臨床　58　(春季増刊)　159-167　2010/04

  68. 多発性骨転移後35年間長期生存している悪性褐色細胞腫の一例

    竹内 陽一, 三島 英換, 鈴木 健弘, 阿部 倫明, 種本 雅之, 阿部 高明, 伊藤 貞嘉

    日本内分泌学会雑誌　86　(1)　156-156　2010/03

    Publisher: (一社)日本内分泌学会

    ISSN： 0029-0661

  69. 【高血圧のすべて】 高血圧の治療 降圧薬による治療 利尿薬 ACE阻害薬・ARB

    三島 英換, 伊藤 貞嘉

    からだの科学　(264)　127-130　2010/02

    Publisher: (株)日本評論社

    ISSN： 0453-3038

  70. 尿細管管腔内酸性化は脂肪酸結合アルブミンによる近位尿細管細胞からの活性酸素産生を増悪させる

    相馬 友和, 阿部 倫明, 秋山 泰利, 豊原 敬文, 塩飽 博美, 竹内 陽一, 三島 英換, 鈴木 健弘, 種本 雅之, 阿部 高明, 伊藤 貞嘉

    日本高血圧学会総会プログラム・抄録集　32回　172-172　2009/10

    Publisher: (NPO)日本高血圧学会

  71. ヒト腎臓特異的有機アニオントランスポーターSLCO4C1の転写活性調節と臨床応用

    鈴木 健弘, 豊原 敬文, 秋山 泰利, 相馬 友和, 竹内 陽一, 三島 英換, 阿部 倫明, 種本 雅之, 伊藤 貞嘉, 阿部 高明

    日本高血圧学会総会プログラム・抄録集　32回　236-236　2009/10

    Publisher: (NPO)日本高血圧学会

  72. 狭窄部血行動態指標と血行再建術による降圧効果の動脈硬化性腎動脈狭窄での検討

    種本 雅之, 竹内 陽一, 三島 英換, 相馬 友和, 秋山 泰利, 豊原 敬文, 鈴木 健弘, 阿部 倫明, 阿部 高明, 伊藤 貞嘉

    日本高血圧学会総会プログラム・抄録集　32回　313-313　2009/10

    Publisher: (NPO)日本高血圧学会

  73. スタチンによる血圧降下作用機序の解析

    豊原 敬文, 秋山 泰利, 竹内 陽一, 三島 英換, 相馬 友和, 鈴木 健弘, 阿部 倫明, 種本 雅之, 曽我 朋義, 伊藤 貞嘉, 阿部 高明

    日本高血圧学会総会プログラム・抄録集　32回　323-323　2009/10

    Publisher: (NPO)日本高血圧学会

  74. Adrenocorticotropic hormone stimulation during adrenal vein sampling. International-journal Peer-reviewed

    Masayuki Tanemoto, Eikan Mishima, Yoichi Takeuchi, Takaaki Abe

    Hypertension (Dallas, Tex. : 1979)　54　(3)　e23; author reply e24　2009/09

    DOI： 10.1161/HYPERTENSIONAHA.109.137141 　

  75. 経皮的腎動脈形成術の適応を決める際の狭窄部圧較差測定の重要性

    三島 英換, 竹内 陽一, 鈴木 健弘, 阿部 倫明, 種本 雅之, 阿部 高明, 伊藤 貞嘉

    日本内分泌学会雑誌　85　(2)　719-719　2009/09

    Publisher: (一社)日本内分泌学会

    ISSN： 0029-0661

  76. レニン-アンジオテンシン系阻害薬と経皮的腎動脈形成術により腎血管性高血圧に伴うネフローゼ症候群が改善した一例

    竹内 陽一, 三島 英換, 鈴木 健弘, 阿部 倫明, 種本 雅之, 阿部 高明, 伊藤 貞嘉

    日本内分泌学会雑誌　85　(2)　724-724　2009/09

    Publisher: (一社)日本内分泌学会

    ISSN： 0029-0661

  77. 腎動脈ステント留置後再狭窄の治療適応判定における腎動脈エコーの有用性

    竹内 陽一, 三島 英換, 秋山 泰利, 豊原 敬文, 鈴木 健弘, 阿部 倫明, 種本 雅之, 阿部 高明, 伊藤 貞嘉

    日本腎臓学会誌　51　(6)　692-692　2009/08

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  78. 副腎静脈を造影できるタイミングでのCT撮影のAVSへの有用性 : 右副腎静脈の解剖学的検討

    三島 英換, 工藤 正孝, 太田 耕造, 壷井 匡浩

    日本内分泌学会雑誌　84　95-97　2008/06/20

    ISSN： 0029-0661

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Industrial Property Rights 2

  1. フェロトーシス抑制剤

    Property Type: Patent

  2. フェロトーシス抑制薬の同定

    Property Type: Patent

Research Projects 17

  1. ながはまコホートおよび佐渡コホートのゲノム情報解析による、尿酸値関連変異の探索

    三澤 計治, 三島 英換, 日笠 幸一郎, 大内 基司, 安西 尚彦, 横関 明男

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 基盤研究(C)

    Category: 基盤研究(C)

    Institution: 関西医科大学

    2020/04/01 - 2023/03/31

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    痛風は、尿酸が原因で起こる関節炎であり、罹患者も多い。先行研究では血清尿酸値の遺伝率は30～70％と推定されている。遺伝子ベース検定を用いた最近の研究では、まれな変異の有無がヒト集団中の血清尿酸値分散に大きく寄与していることが示唆されている。遺伝子ベース検定は、1つの遺伝子に含まれる複数の遺伝子変異の影響を1回の検定で考慮するものである。本研究課題では、数値計算を用い、遺伝子ベース検定のサンプルサイズと検出力の関係を解析した。仮想的なヒト集団を、まれな変異を持つ人々と持たない人々の二つの群に分けた。この二群間での尿酸値の平均値の差は、先行研究によるURAT1変異の有無によって生じる差と同じ値を使った。また、各群の人々の尿酸値は、その人が属する群の平均値を期待値とする正規分布に従うと仮定した。等分散性を仮定しないWelchのt検定を行い、検出力を計算した。今回の数値計算から、まれな変異は、一つのサイトだけを用いている場合、1万人から数万人ほどの大きさのサンプルが必要であることがわかった。複数のSNPをまとめた検定を行うことで、検出力が上がり、数百から数千人規模の研究でも検出できることが示された。この研究は、今まで主に研究対象となってきた「ありふれた疾患、ありふれた変異」に加え、遺伝子ベース検定による、「ありふれた疾患、まれな変異」の研究の可能性を示した。

  2. Lipid radicals in regulation of ferroptosis

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Fund for the Promotion of Joint International Research (Fostering Joint International Research (A))

    Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research (A))

    Institution: Tohoku University

    2021 - 2023

  3. 生命進化における抗フェロトーシスビタミンとしてのビタミンKの役割と治療応用

    System: JST創発的研究支援事業（第3期）

    2023 -

  4. 応用酵素協会 成人病の病因・病態の解明に関する研究助成 Competitive

    三島 英換

    2016 - 2022

  5. Gut-renal axis: microbiota and chronic kidney disease

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Tohoku University

    2018/04/01 - 2021/03/31

  6. Development of a disease risk estimation model with genetic and environmental factors for uric acid level.

    MISAWA Kazuharu

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

    Category: Grant-in-Aid for Scientific Research (C)

    2017/04/01 - 2020/03/31

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    Gout is a common arthritis caused by monosodium urate crystals. The heritability of serum urate levels is estimated to be 30% - 70%; however, common genetic variants account for only 7.9% of the variance in serum urate levels. This discrepancy is an example of missing heritability. The missing heritability suggests that variants associated with uric acid levels are yet to be found. By using genomic sequences of the ToMMo cohort, we identified rare variants of the SLC22A12 gene which encodes a urate transporter called URAT1. We identified new variants and carried out experiments to examine whether they affect the resulting protein variants. We grouped the participants with variants affecting urate uptake by URAT1 and analyzed the variance of serum urate levels. The results showed that the heritability explained by the SLC22A12 variants of men and women exceeds 10%, suggesting that rare variants underlie a substantial portion of the missing heritability of serum

  7. 公益財団法人 冲中記念成人病研究所 研究助成

    2020 -

  8. 公益財団法人 ひと・健康・未来研究財団 研究助成

    2019 -

  9. 公益財団法人 石橋由紀子記念基金 研究助成

    2019 -

  10. Gut-renal axis: microbiota and chronic kidney disease

    Eikan Mishima

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)

    Category: Grant-in-Aid for Young Scientists (B)

    Institution: Tohoku University

    2016/04/01 - 2018/03/31

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    Microbiota is involved in pathophysiology of renal disease such as accumulation of uremic solutes. We compared renal failure and control mice under germ-free or specific pathogen-free (SPF) conditions, examining the metabolite profiles using CE-TOFMS. We revealed that 11 solutes were considered microbiota-derived uremic solutes. Additionally, germ-free renal failure conditions resulted in the disappearance of colonic short-chain fatty acids, decreased utilization of intestinal amino acids, and more severe renal damage compared with SPF mice with renal failure. Thus, microbiota contributes to the production of harmful uremic solutes, but conversely, growth without microbiota has harmful effects on CKD progression. We examined the effect of canagliflozin, a SGLT inhibitor, on the accumulation of uremic toxins using renal failure mice. Canagliflozin treatment significantly reduced the plasma levels of p-cresyl sulfate and indoxyl sulfate and altered the microbiota composition.

  11. 腸腎連関の解明による慢性腎臓病の新規治療介入法への応用 Competitive

    三島 英換

    Offer Organization: 弘美医学研究助成基金

    2017 - 2018

  12. 慢性腎臓病の腎内炎症における腸内細菌叢の関与の検討 Competitive

    三島 英換

    Offer Organization: 宮城腎臓協会

    System: 公募研究

    2017 - 2018

  13. - Competitive

    2016 - 2017

  14. Conformational change in transfer RNA is an early indicator of acute cellular damage

    Mishima Eikan

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)

    Category: Grant-in-Aid for Young Scientists (B)

    Institution: Tohoku University

    2014/04/01 - 2016/03/31

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    We revealed that the detection of 1-methyladenosine, which is a modified nucleoside containing in transfer RNA, is a useful new biomarker for diagnosis of acute kidney injury (Mishima et al. JASN, 2014). In addition, we showed that circulating 1-methyladenosine levels are significantly associated with the mortality in the general population using the sample of Ohasama cohort study. Therefore, tRNA damage reflects early oxidative stress damage, and detection of tRNA damage may be a useful tool for identifying organ damage and forming a clinical prognosis. Furthermore, we developed a method for detecting RNA modifications called immuno-northern blotting analysis and confirmed its various capabilities (Mishima et al. PLoS ONE, 2015).

  15. NM-Global COE program 研究助成

    2011 -

  16. NM-Global COE program 研究助成

    2010 -

  17. NM-Global COE program 研究助成

    2009 -

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Teaching Experience 6

  1. Hygiene　Tohoku University

  2. 宮城教育大学 学部講義「腸内細菌叢と疾患」

  3. 東北大学医学部 系統講義「電解質・酸塩基平衡」（学部4年生向け）

  4. 東北大学医学部 チュートリアル講義（学部4年生向け）

  5. 東北大学 全学教育 基礎ゼミ 「生体の恒常性を保つ仕組み」

  6. 東北大学歯学部 隣接講義「高血圧」

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Other 1

  1. 専門医資格

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    日本内科学会（総合内科専門医）、日本腎臓学会（評議員、指導医、専門医）、日本内分泌学会（内分泌専門医）、日本高血圧学会（指導医、高血圧専門医）、プライマリケア連合学会（認定指導医）