TOHOKU UNIVERSITY Researchers - Nobuyuki Takahashi

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Nobuyuki Takahashi

Section

Graduate School of Pharmaceutical Sciences

Job title

Professor

Degree

医学博士 (Tohoku University)

researchmap

https://researchmap.jp/nobudon1006

J-GLOBAL ID

201101041627935832

Research History 5

2019/10 - Present

Tohoku University　Graduate School of Medicine
2019/10 - Present

Tohoku University Graduate School of Pharmaceutical Sciences　Division of Clinical Pharmacy and Therapeutics　Professor
1997/10 - Present

University of North Carolina at Chapel Hill
2010/08 - 2019/09

Tohoku University　Graduate School of Medicine
2010/08 - 2019/09

Tohoku University　Graduate School of Pharmaceutical Sciences

Education 3

university of North Carolina at Chapel Hill　School of Medicine Department of Pathology and Laboratory Medicine

1996/10 - 1997/08
Tohoku University　Graduate School of Medicine

1990/04 - 1995/04
Tohoku University　Faculty of Medicine

1983/04 - 1989/03

Committee Memberships 2

日本妊娠高血圧学会　評議員

2018 - Present
日本高血圧学会　評議員

- Present

Research Interests 5

hypertension
metabolic syndrome
kidney disease
diabetic nephropathy
preeclampsia, hypertensive disease of pregnancy

Research Areas 8

Life sciences / Physiology /
Life sciences / Clinical pharmacy /
Life sciences / Pharmacology /
Life sciences / Developmental biology /
Life sciences / Metabolism and endocrinology /
Life sciences / Laboratory animal science /
Life sciences / Nephrology /
Life sciences / Obstetrics and gynecology /

Awards 7

Award of Excellence in Renal Physiology

2020　American Physiological Society　Dual blockade of protease-activated receptor 1 and 2 additively ameliorates diabetic kidney disease. Am J Physiol 2020 May 1;318(5):F1067-F1073
東北大学薬学研究科科長賞（研究面）

2017　東北大学薬学研究科
東北大学医学部奨学賞金賞

2017　東北大学医学部　妊娠高血圧腎症の新規薬物治療の開発
Poster Award of Angiotensin

2008　Gordon Research Conference
東北大学医学部奨学賞銀賞

1996　東北大学医学部　ヘンレの細い上行脚のNaCl輸送とその調節
若手研究者賞

1994　米国腎臓学会
Young Investigator Award

1992

Show all ︎Show 5

Papers 174

Nicotinamide Attenuates Complement and Coagulation Pathways and Resultant Renal Fibrosis. International-journal

Saori Kin, Yuji Oe, Taku Obara, Emiko Sato, Nobuyuki Takahashi, Mariko Miyazaki, Tetsuhiro Tanaka

FASEB journal : official publication of the Federation of American Societies for Experimental Biology　39　(23)　e71263　2025/12/15

DOI： 10.1096/fj.202502028R 　

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The coagulation and complement pathways interact with each other, promoting inflammation and increasing thrombotic risk. However, their roles in chronic kidney disease (CKD) remain unclear. In our CKD cohort, elevated plasma fibrinogen and shortened prothrombin time were associated with higher serum complement C3 and C4 levels. Moreover, gene expression analysis of CKD renal tissues in public databases showed a positive correlation between fibrinogen β chain and C3 expression levels. Finally, tissue factor (factor III), fibrinogen, and C3 deposition and the genes related to coagulation and complement cascades were upregulated in fibrotic kidneys of mice treated with adenine or folic acid. To explore the modulators of these systems, the therapeutic effects of nicotinamide (NAM), a NAD+ precursor with anti-inflammatory and antithrombotic properties, were investigated. KEGG pathway analysis with RNA sequencing identified a significant inhibition of coagulation and complement cascades by NAM administration in adenine-induced nephropathy. Moreover, NAM suppressed innate immune responses associated with the prothrombotic state, including inflammasome and neutrophil extracellular trap formation. Collectively, these results suggest that excessive coagulation and complement activities are involved in the pathogenesis of CKD and are modulated by NAM.
慢性腎臓病のサルコペニアにおける骨格筋のメタボローム解析

原秋夕希, 三枝大輔, 山越聖子, 高橋信行, 佐藤恵美子

JSBMS Letters　50　(Suppl.)　59-59　2025/08
Publisher: (一社)日本医用マススペクトル学会
ISSN： 1881-5464
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
慢性腎臓病における凝固・補体経路の役割とnicotinamideの治療効果

金沙織, 大江佑治, 小原拓, 佐藤恵美子, 高橋信行, 田中哲洋

日本腎臓学会誌　67　(4)　475-475　2025/06
Publisher: (一社)日本腎臓学会
ISSN： 0385-2385

eISSN： 1884-0728
モデルマウスを用いた慢性腎臓病合併サルコペニアの病態解明

原秋夕希, 三枝大輔, 山越聖子, 高橋信行, 佐藤恵美子

日本腎臓学会誌　67　(4)　532-532　2025/06
Publisher: (一社)日本腎臓学会
ISSN： 0385-2385

eISSN： 1884-0728
アドリアマイシン誘発性腎症へのニコチンアミドの効果の検討

大金美月, 高橋慧, 山越聖子, 高橋信行, 佐藤恵美子

日本腎臓学会誌　67　(4)　532-532　2025/06
Publisher: (一社)日本腎臓学会
ISSN： 0385-2385

eISSN： 1884-0728
慢性腎臓病における凝固・補体経路の役割とnicotinamideの治療効果

金沙織, 大江佑治, 小原拓, 佐藤恵美子, 高橋信行, 田中哲洋

日本腎臓学会誌　67　(4)　475-475　2025/06
Publisher: (一社)日本腎臓学会
ISSN： 0385-2385

eISSN： 1884-0728
モデルマウスを用いた慢性腎臓病合併サルコペニアの病態解明

原秋夕希, 三枝大輔, 山越聖子, 高橋信行, 佐藤恵美子

日本腎臓学会誌　67　(4)　532-532　2025/06
Publisher: (一社)日本腎臓学会
ISSN： 0385-2385

eISSN： 1884-0728
Nicotinamide ameliorates podocyte injury and albuminuria in adriamycin-induced nephropathy. International-journal

Kei Takahashi, Emiko Sato, Seiko Yamakoshi, Mizuki Ogane, Akiyo Sekimoto, Takamasa Ishikawa, Kiyomi Kisu, Yuji Oe, Koji Okamoto, Mariko Miyazaki, Tetsuhiro Tanaka, Nobuyuki Takahashi

American journal of physiology. Renal physiology　2025/03/04

DOI： 10.1152/ajprenal.00297.2024 　

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Podocytes are key components of the glomerular filtration barrier, and their injury leads to proteinuria, chronic kidney disease (CKD), and nephrotic syndrome. Effective treatments for these conditions are not well established, and prevention of podocyte injury is a crucial challenge. Nicotinamide (NAM), a form of vitamin B3, has been reported to exert beneficial effects in various renal disease models due to its antioxidant and anti-inflammatory properties and its ability to replenish nicotinamide adenine dinucleotide (NAD+). However, its impact on adriamycin (ADR)-induced nephropathy, a model of nephrotic syndrome caused by podocyte injury, remains unclear. We investigated the effects of NAM administration in a mouse model of ADR nephropathy. BALB/c mice were intravenously administered ADR to induce nephropathy. In the NAM-treated group, mice received 0.6% NAM in drinking water ad libitum starting 7 days before ADR administration. After 14 days, NAM treatment decreased albuminuria, glomerular sclerosis, and podocyte injury, and reduced inflammation and oxidative stress markers in the kidneys. NAM and NAD+ levels were decreased in ADR-treated kidneys, and the expression of the NAD+-consuming enzymes SIRT1 and PARP-1 was decreased and increased, respectively. Nicotinamide N-methyltransferase expression was increased. NAM canceled these abnormalities. In cultured rat podocytes, NAD+ alleviated ADR-induced cytotoxicity, apoptosis, and inflammation. These findings suggest that NAM prevents ADR nephropathy and podocyte injury, likely through NAD+ replenishment.
The Many Faces of Protease-Activated Receptor 2 in Kidney Injury. International-journal

Yuji Oe, Tetsuhiro Tanaka, Nobuyuki Takahashi

Biomedicines　13　(2)　2025/02/08

DOI： 10.3390/biomedicines13020414 　

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Protease-activated receptor 2 (PAR2) is a seven-transmembrane, G-protein-coupled receptor that is activated by coagulation proteases such as factor VIIa and factor Xa and other serine proteases. It is a potential therapeutic target for kidney injury, as it enhances inflammatory and fibrotic responses via the nuclear factor-kappa B and mitogen-activated protein kinase cascades. The body of knowledge regarding the role of PAR2 in kidney disease is currently growing, and its role in various kidney disease models, such as acute kidney injury, renal fibrosis, diabetic kidney disease, aging, and thrombotic microangiopathy, has been reported. Here, we review the literature to better understand the various aspects of PAR2 in kidney disease.
Impacts of low birthweight on kidney development and intergenerational growth of the offspring

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　111159-111159　2024/10
Publisher: Elsevier BV
DOI： 10.1016/j.isci.2024.111159 　

ISSN： 2589-0042
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
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
Tissue Factor, Thrombosis, and Chronic Kidney Disease. International-journal

Yuji Oe, Nobuyuki Takahashi

Biomedicines　10　(11)　2022/10/28

DOI： 10.3390/biomedicines10112737 　

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Coagulation abnormalities are common in chronic kidney disease (CKD). Tissue factor (TF, factor III) is a master regulator of the extrinsic coagulation system, activating downstream coagulation proteases, such as factor Xa and thrombin, and promoting fibrin formation. TF and coagulation proteases also activate protease-activated receptors (PARs) and are implicated in various organ injuries. Recent studies have shown the mechanisms by which thrombotic tendency is increased under CKD-specific conditions. Uremic toxins, such as indoxyl sulfate and kynurenine, are accumulated in CKD and activate TF and coagulation; in addition, the TF-coagulation protease-PAR pathway enhances inflammation and fibrosis, thereby exacerbating renal injury. Herein, we review the recent research studies to understand the role of TF in increasing the thrombotic risk and CKD progression.
Tadalafil投与が子宮灌流圧低下マウスの仔の出生体重と腎発達不全に与える影響

猿山春花, 堰本晃代, 高相陽子, 高橋信行, 佐藤恵美子

DOHaD研究　10　(2)　48-48　2022/10
Publisher: (一社)日本DOHaD学会
ISSN： 2187-2562

eISSN： 2187-2597
低出生体重が及ぼす将来の妊娠への影響モデルマウスを用いた胎仔および胎盤の評価

山本真莉, 堰本晃代, 大川雅敬, 高橋信行, 佐藤恵美子

DOHaD研究　10　(2)　49-49　2022/10
Publisher: (一社)日本DOHaD学会
ISSN： 2187-2562

eISSN： 2187-2597
低出生体重が及ぼす将来の妊娠への影響モデルマウスを用いた母体の評価

大川雅敬, 堰本晃代, 山本真莉, 高橋信行, 佐藤恵美子

DOHaD研究　10　(2)　50-50　2022/10
Publisher: (一社)日本DOHaD学会
ISSN： 2187-2562

eISSN： 2187-2597
ラクトフェリン投与による慢性腎臓病およびその合併症の進行抑制効果

岩本千奈, 堰本晃代, 高橋信行, 佐藤恵美子

日本腎臓学会誌　64　(3)　221-221　2022/05
Publisher: (一社)日本腎臓学会
ISSN： 0385-2385

eISSN： 1884-0728
ラクトフェリン投与による慢性腎臓病およびその合併症の進行抑制効果

岩本千奈, 堰本晃代, 高橋信行, 佐藤恵美子

日本腎臓学会誌　64　(3)　221-221　2022/05
Publisher: (一社)日本腎臓学会
ISSN： 0385-2385

eISSN： 1884-0728
Methylglyoxal Induces Inflammation, Metabolic Modulation and Oxidative Stress in Myoblast Cells. International-journal

Sota Todoriki, Yui Hosoda, Tae Yamamoto, Mayu Watanabe, Akiyo Sekimoto, Hiroshi Sato, Takefumi Mori, Mariko Miyazaki, Nobuyuki Takahashi, Emiko Sato

Toxins　14　(4)　2022/04/07

DOI： 10.3390/toxins14040263 　

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Uremic sarcopenia is a serious clinical problem associated with physical disability and increased morbidity and mortality. Methylglyoxal (MG) is a highly reactive, dicarbonyl uremic toxin that accumulates in the circulatory system in patients with chronic kidney disease (CKD) and is related to the pathology of uremic sarcopenia. The pathophysiology of uremic sarcopenia is multifactorial; however, the details remain unknown. We investigated the mechanisms of MG-induced muscle atrophy using mouse myoblast C2C12 cells, focusing on intracellular metabolism and mitochondrial injury. We found that one of the causative pathological mechanisms of uremic sarcopenia is metabolic flow change to fatty acid synthesis with MG-induced ATP shortage in myoblasts. Evaluation of cell viability revealed that MG showed toxic effects only in myoblast cells, but not in myotube cells. Expression of mRNA or protein analysis revealed that MG induces muscle atrophy, inflammation, fibrosis, and oxidative stress in myoblast cells. Target metabolomics revealed that MG induces metabolic alterations, such as a reduction in tricarboxylic acid cycle metabolites. In addition, MG induces mitochondrial morphological abnormalities in myoblasts. These changes resulted in the reduction of ATP derived from the mitochondria of myoblast cells. Our results indicate that MG is a pathogenic factor in sarcopenia in CKD.
Myeloid cell-derived coagulation tissue factor is associated with renal tubular damage in mice fed an adenine diet International-journal

Shu Yamakage, Yuji Oe, Emiko Sato, Koji Okamoto, Akiyo Sekimoto, Satoshi Kumakura, Hiroshi Sato, Mai Yoshida, Tasuku Nagasawa, Mariko Miyazaki, Sadayoshi Ito, Nigel Mackman, Nobuyuki Takahashi

Scientific Reports　11　(1)　12159-12159　2021/12
Publisher: Springer Science and Business Media LLC
DOI： 10.1038/s41598-021-91586-5 　

eISSN： 2045-2322

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<title>Abstract</title>Patients with chronic kidney disease (CKD) commonly exhibit hypercoagulability. Increased levels of uremic toxins cause thrombogenicity by increasing tissue factor (TF) expression and activating the extrinsic coagulation cascade. TF is induced in monocytes and macrophages under pathological conditions, such as inflammatory diseases. However, the role of monocyte myeloid cell TF in CKD progression remains unclear. We aimed to clarify this issue, and the present study found that patients with CKD had elevated levels of D-dimer, a marker of fibrin degradation, which was associated with decreased estimated glomerular filtration rate and increased serum levels of uremic toxins, such as indoxyl sulfate. In vitro studies showed that several uremic toxins increased cellular TF levels in monocytic THP-1 cells. Mice with TF specifically deleted in myeloid cells were fed an adenine diet to cause uremic kidney injury. Myeloid TF deletion reduced tubular injury and pro-inflammatory gene expression in the kidneys of adenine-induced CKD but did not improve renal function as measured by plasma creatinine or blood urea nitrogen. Collectively, our findings suggest a novel concept of pathogenesis of coagulation-mediated kidney injury, in which elevated TF levels in monocytes under uremic conditions is partly involved in the development of CKD.
凝固活性と関連する尿毒素の網羅的検討

山陰周, 大江佑治, 佐藤恵美子, 堰本晃代, 宮崎真理子, 佐藤博, 伊藤貞嘉, 高橋信行

日本腎臓学会誌　63　(4)　458-458　2021/06
Publisher: (一社)日本腎臓学会
ISSN： 0385-2385

eISSN： 1884-0728
ウレミックトキシンが凝固線溶系因子発現に及ぼす影響

大江佑治, 佐藤恵美子, 佐藤博, 宮崎真理子, 伊藤貞嘉, 高橋信行

日本腎臓学会誌　63　(4)　510-510　2021/06
Publisher: (一社)日本腎臓学会
ISSN： 0385-2385

eISSN： 1884-0728
凝固活性と関連する尿毒素の網羅的検討

山陰周, 大江佑治, 佐藤恵美子, 堰本晃代, 宮崎真理子, 佐藤博, 伊藤貞嘉, 高橋信行

日本腎臓学会誌　63　(4)　458-458　2021/06
Publisher: (一社)日本腎臓学会
ISSN： 0385-2385

eISSN： 1884-0728
ウレミックトキシンが凝固線溶系因子発現に及ぼす影響

大江佑治, 佐藤恵美子, 佐藤博, 宮崎真理子, 伊藤貞嘉, 高橋信行

日本腎臓学会誌　63　(4)　510-510　2021/06
Publisher: (一社)日本腎臓学会
ISSN： 0385-2385

eISSN： 1884-0728
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　2021/02

DOI： 10.1016/j.heliyon.2021.e06221 　

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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.
Lack of Endothelial Nitric Oxide Synthase Accelerates Ectopic Calcification in Uremic Mice Fed an Adenine and High Phosphorus Diet. International-journal

Yuji Oe, Shohei Mitsui, Emiko Sato, Naoko Shibata, Kiyomi Kisu, Akiyo Sekimoto, Mariko Miyazaki, Hiroshi Sato, Sadayoshi Ito, Nobuyuki Takahashi

The American journal of pathology　191　(2)　283-293　2021/02

DOI： 10.1016/j.ajpath.2020.10.012 　

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Ectopic calcification is a risk of cardiovascular disease in chronic kidney disease (CKD) patients, and impaired endothelial nitric oxide synthase (eNOS) is involved in the CKD complications. However, whether eNOS dysfunction is a cause of ectopic calcification in CKD remains to be elucidated. To address this issue, we investigated the role of eNOS in ectopic calcification in mice with renal injury caused by an adenine and high-phosphorus (Ade + HP) diet. DBA/2J mice, a calcification-sensitive strain, were fed Ade + HP for 3 weeks. Expression levels of eNOS-related genes were reduced significantly in their calcified aorta. C57BL/6J is a calcification-resistant strain, and wild-type mice showed mild calcified lesions in the aorta and kidney when given an Ade + HP diet for 4 weeks. In contrast, a lack of eNOS led to the development of severe aortic calcification accompanied by an increase in runt-related transcription factor 2, an osteochondrogenic marker. Increased renal calcium deposition and the tubular injury score were remarkable in mice lacking eNOS-fed Ade + HP. Exacerbation of ectopic calcification by a lack of eNOS is associated with increased oxidative stress markers such as nicotinamide adenine dinucleotide phosphate oxidases. In conclusion, eNOS is critically important in preventing ectopic calcification. Therefore, the maintenance of eNOS is useful to reduce cardiovascular disease events and to improve prognosis in CKD patients.
Nicotinamide Attenuates the Progression of Renal Failure in a Mouse Model of Adenine-Induced Chronic Kidney Disease. International-journal

Satoshi Kumakura, Emiko Sato, Akiyo Sekimoto, Yamato Hashizume, Shu Yamakage, Mariko Miyazaki, Sadayoshi Ito, Hideo Harigae, Nobuyuki Takahashi

Toxins　13　(1)　2021/01/11

DOI： 10.3390/toxins13010050 　

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Nicotinamide adenine dinucleotide (NAD+) supplies energy for deoxidation and anti-inflammatory reactions fostering the production of adenosine triphosphate (ATP). The kidney is an essential regulator of body fluids through the excretion of numerous metabolites. Chronic kidney disease (CKD) leads to the accumulation of uremic toxins, which induces chronic inflammation. In this study, the role of NAD+ in kidney disease was investigated through the supplementation of nicotinamide (Nam), a precursor of NAD+, to an adenine-induced CKD mouse model. Nam supplementation reduced kidney inflammation and fibrosis and, therefore, prevented the progression of kidney disease. Notably, Nam supplementation also attenuated the accumulation of glycolysis and Krebs cycle metabolites that occurs in renal failure. These effects were due to increased NAD+ supply, which accelerated NAD+-consuming metabolic pathways. Our study suggests that Nam administration may be a novel therapeutic approach for CKD prevention.
Coagulation, Protease-Activated Receptors, and Diabetic Kidney Disease: Lessons from eNOS-Deficient Mice

Yuji Oe, Mariko Miyazaki, Nobuyuki Takahashi

The Tohoku Journal of Experimental Medicine　255　(1)　1-8　2021
Publisher: Tohoku University Medical Press
DOI： 10.1620/tjem.255.1 　

ISSN： 0040-8727

eISSN： 1349-3329

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Endothelial nitric oxide synthase (eNOS) dysfunction is known to exacerbate the progression and prognosis of diabetic kidney disease (DKD). One of the mechanisms through which this is achieved is that low eNOS levels are associated with hypercoagulability, which promotes kidney injury. In the extrinsic coagulation cascade, the tissue factor (factor III) and downstream coagulation factors, such as active factor X (FXa), exacerbate inflammation through activation of the protease-activated receptors (PARs). Recently, it has been shown that the lack of or reduced eNOS expression in diabetic mice, as a model of advanced DKD, increases renal tissue factor levels and PAR1 and 2 expression in their kidneys. Furthermore, pharmaceutical inhibition or genetic deletion of coagulation factors or PARs ameliorated inflammation in DKD in mice lacking eNOS. In this review, we summarize the relationship between eNOS, coagulation, and PARs and propose a novel therapeutic option for the management of patients with DKD.
The effect of aldosterone on adiposity - The role of glucose absorption in the small intestine. International-journal

Hidekazu Shirai, Emiko Sato, Akiyo Sekimoto, Taeko Uchida, Yuji Oe, Sadayoshi Ito, Hiroshi Sato, Nobuyuki Takahashi

Biochemical and biophysical research communications　531　(4)　628-635　2020/10/22

DOI： 10.1016/j.bbrc.2020.07.119 　

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We have previously demonstrated that manipulation of the renin angiotensin system (RAS) has large effects on digestive efficiency. However, the effects of aldosterone on body weight, adiposity, and glucose absorption in the intestine remains unknown. We here demonstrated that lack of aldosterone synthase (ASKO) in mice did not affect adiposity. In contrast, mice administered with aldosterone were resistant to diet-induced obesity. This is due to gastrointestinal loss of dietary glucose. As expected, ASKO mice had increased glucose absorption, whereas mice administered with aldosterone had reduced glucose absorption in the small intestine. Furthermore, the level of protein expression of sodium glucose transporter 1 (SGLT1) in the mucosa of the jejunum was higher in ASKO mice, and lower in mice administered with aldosterone than control mice. Our findings indicate that aldosterone plays an important role on SGLT-1-mediated glucose absorption in the small intestine.
Protease-activated receptor 2 contributes to placental development and fetal growth in mice. International-journal Peer-reviewed

Shu Yamakage, Yuji Oe, Akiyo Sekimoto, Hirofumi Obata, Miho Yasuta, Emiko Sato, Satoshi Kumakura, Hiroshi Sato, Junichi Sugawara, Sadayoshi Ito, Nobuyuki Takahashi

Thrombosis research　193　173-179　2020/09

DOI： 10.1016/j.thromres.2020.06.039 　

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BACKGROUND: Protease-activated receptor 2 (PAR2) is activated by serine proteases such as coagulation tissue factor/VIIa complex, factor Xa or trypsin and is pro-angiogenic in several disease models. Impaired angiogenesis in placenta causes placental dysfunction and fetal growth restriction. PAR2 is expressed in the placenta trophoblast. However, the role of PAR2 in pregnancy remains unknown. OBJECTIVE: The present study aimed to examine the role of PAR2 in placental development and fetal growth using a murine model. METHODS: PAR2-/- or PAR2+/+ mice in the ICR background were used. Female PAR2-/- mice were mated with male PAR2-/- mice, and female PAR2+/+ mice were mated with male PAR2+/+ mice to obtain PAR2-/- and PAR2+/+ fetuses, respectively. The day a virginal plug was observed in the morning was determined as 0.5-day post-coitum (dpc). Pregnant mice were sacrificed on 13.5 or 18.5 dpc to collect samples. RESULTS: A deficiency of PAR2 significantly reduced the fetal and placental weight and impaired placental labyrinth development in mice on 18.5 dpc. Collagen IV expression in placenta labyrinth was smaller in PAR2 knockout mice compared to that of wild-type mice. A deficiency of PAR2 also reduced the expression levels of genes related to angiogenesis and coagulation in placenta. CONCLUSION: Our data suggest that PAR2 is required for fetal growth and angiogenesis in the placenta and is thus important for a normal pregnancy.
Metabolomics of a mouse model of preeclampsia induced by overexpressing soluble fms-like tyrosine kinase 1. International-journal Peer-reviewed

Emiko Sato, Yukako Tsunokuni, Manami Kaneko, Daisuke Saigusa, Ritsumi Saito, Shuichi Shimma, Akiyo Sekimoto, Yoshiko Kawana, Yuji Oe, Sadayoshi Ito, Hiroshi Sato, Nobuyuki Takahashi

Biochemical and biophysical research communications　527　(4)　1064-1071　2020/07/05

DOI： 10.1016/j.bbrc.2020.04.079 　

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Preeclampsia (PE) is a leading cause of maternal morbidity and mortality. Nicotinamide has beneficial effects on PE. In this study, we evaluated the effect of nicotinamide on placental development using a PE mouse model. To generate the PE model, a recombinant adenovirus to overproduce soluble fms-like tyrosine kinase 1 (sFlt-1) was administered to mice (Jcl:ICR) at 8.5 day post-coitum (dpc). Plasma and placenta samples were harvested at 12.5 dpc. Fetal and placental weight was significantly decreased at 12.5 dpc in PE mice. Plasma and placental acylcarnitine levels were significantly higher in PE mice than those in control mice. Glycolysis was accelerated and glucose metabolic flow was altered with hypoxia, leading to ATP shortage in the labyrinth of PE mice. In PE mice, ATP production was diminished, and fatty acid oxidation was accelerated in the placenta, consequently, blood carnitine and acylcarnitine levels were increased. The mitochondrial morphology in BeWo cells was impaired under hypoxia. Nicotinamide treatment reversed fetal growth restriction, placental development, and altered metabolic flow in the early stage in PE. In addition, nicotinamide normalized impaired mitochondrial morphology. Hence, targeting this metabolic alteration in the placenta using nicotinamide may serve as a potential therapeutic approach for PE treatment.
単球・マクロファージ由来組織因子の慢性腎臓病における役割

山陰周, 大江佑治, 佐藤恵美子, 堰本晃代, 岡本好司, 宮崎真理子, 佐藤博, 伊藤貞嘉, 高橋信行

日本腎臓学会誌　62　(4)　284-284　2020/07
Publisher: (一社)日本腎臓学会
ISSN： 0385-2385

eISSN： 1884-0728
内皮型NO合成酵素欠損はCKD関連異所性石灰化を誘導する

大江佑治, 佐藤恵美子, 宮崎真理子, 岡本好司, 佐藤博, 伊藤貞嘉, 高橋信行

日本腎臓学会誌　62　(4)　285-285　2020/07
Publisher: (一社)日本腎臓学会
ISSN： 0385-2385

eISSN： 1884-0728
ニコチンアミドは炎症の抑制によりアデニン腎症発生を予防する

熊倉慧, 佐藤恵美子, 堰本晃代, 大江佑治, 宮崎真理子, 高橋信行

日本腎臓学会誌　62　(4)　335-335　2020/07
Publisher: (一社)日本腎臓学会
ISSN： 0385-2385

eISSN： 1884-0728
Oral high dose vitamin B12 decreases renal superoxide and post-ischemia/reperfusion injury in mice. International-journal

Feng Li, Edward M Bahnson, Jennifer Wilder, Robin Siletzky, John Hagaman, Volker Nickekeit, Sylvia Hiller, Azraa Ayesha, Lanfei Feng, Jerrold S Levine, Nobuyuki Takahashi, Nobuyo Maeda-Smithies

Redox biology　32　101504-101504　2020/05

DOI： 10.1016/j.redox.2020.101504 　

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Renal ischemia/reperfusion injury (IRI) is a leading cause of acute kidney injury (AKI), a potentially fatal syndrome characterized by a rapid decline in kidney function. Excess production of superoxide contributes to the injury. We hypothesized that oral administration of a high dose of vitamin B12 (B12 - cyanocobalamin), which possesses a superoxide scavenging function, would protect kidneys against IRI and provide a safe means of treatment. Following unilateral renal IR surgery, C57BL/6J wild type (WT) mice were administered B12 via drinking water at a dose of 50 mg/L. After 5 days of the treatment, plasma B12 levels increased by 1.2-1.5x, and kidney B12 levels increased by 7-8x. IRI mice treated with B12 showed near normal renal function and morphology. Further, IRI-induced changes in RNA and protein markers of inflammation, fibrosis, apoptosis, and DNA damage response (DDR) were significantly attenuated by at least 50% compared to those in untreated mice. Moreover, the presence of B12 at 0.3 μM in the culture medium of mouse proximal tubular cells subjected to 3 hr of hypoxia followed by 1 hr of reperfusion in vitro showed similar protective effects, including increased cell viability and decreased reactive oxygen species (ROS) level. We conclude that a high dose of B12 protects against perfusion injury both in vivo and in vitro without observable adverse effects in mice and suggest that B12 merits evaluation as a treatment for I/R-mediated AKI in humans.
Dual blockade of protease-activated receptor 1 and 2 additively ameliorates diabetic kidney disease. International-journal

Shohei Mitsui, Yuji Oe, Akiyo Sekimoto, Emiko Sato, Yamato Hashizume, Shu Yamakage, Satoshi Kumakura, Hiroshi Sato, Sadayoshi Ito, Nobuyuki Takahashi

American journal of physiology. Renal physiology　318　(5)　F1067-F1073　2020/05/01

DOI： 10.1152/ajprenal.00595.2019 　

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Protease-activated receptors (PARs) are coagulation protease targets, and they increase expression of inflammatory cytokines and chemokines in various diseases. Of all PARs, previous reports have shown that PAR1 or PAR2 inhibition is protective against diabetic glomerular injury. However, how PAR1 and PAR2 cooperatively contribute to diabetic kidney disease (DKD) pathogenesis and whether dual blockade of PARs is more effective in DKD remain elusive. To address this issue, male type I diabetic Akita mice heterozygous for endothelial nitric oxide synthase were used as a model of DKD. Mice (4 mo old) were divided into four treatment groups and administered vehicle, PAR1 antagonist (E5555, 60 mg·kg-1·day-1), PAR2 antagonist (FSLLRY, 3 mg·kg-1·day-1), or E5555 + FSLLRY for 4 wk. The results showed that the urinary albumin creatinine ratio was significantly reduced when both PAR1 and PAR2 were blocked with E5555 + FSLLRY compared with the vehicle-treated group. Dual blockade of PAR1 and PAR2 by E5555 + FSLLRY additively ameliorated histological injury, including mesangial expansion, glomerular macrophage infiltration, and collagen type IV deposition. Marked reduction of inflammation- and fibrosis-related gene expression in the kidney was also observed. In vitro, PAR1 and PAR2 agonists additively increased mRNA expression of macrophage chemoattractant protein 1 or plasminogen activator inhibitor-1 in human endothelial cells. Changes induced by the PAR1 agonist were blocked by a NF-κB inhibitor, whereas those of the PAR2 agonist were blocked by MAPK and/or NF-κB inhibitors. These findings suggest that PAR1 and PAR2 additively contribute to DKD pathogenesis and that dual blockade of both could be a novel therapeutic option for treatment of patients with DKD.
Uremic toxins alter coagulation and fibrinolysis-related genes expression in human endothelial cells. International-journal

Yuji Oe, Emiko Sato, Hiroshi Sato, Mariko Miyazaki, Sadayoshi Ito, Nobuyuki Takahashi

Thrombosis research　186　75-77　2020/02

DOI： 10.1016/j.thromres.2019.12.017 　
Tadalafil alleviates preeclampsia and fetal growth restriction in RUPP model of preeclampsia in mice. International-journal Peer-reviewed

Akiyo Sekimoto, Kayo Tanaka, Yamato Hashizume, Emiko Sato, Hiroshi Sato, Tomoaki Ikeda, Nobuyuki Takahashi

Biochemical and biophysical research communications　521　(3)　769-774　2020/01/15

DOI： 10.1016/j.bbrc.2019.10.186 　

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BACKGROUND: - Tadalafil, a long-acting phosphodiesterase 5 (PDE5) inhibitor, alleviates preeclampsia (PE), and decreases the fetal and infant deaths associated with fetal growth restriction (FGR) in phase II clinical trial. Recently, we demonstrated that tadalafil alleviates FGR and hypertension in the dams with PE induced by l-NAME. OBJECTIVE: -The aim of present study was to clarify the effect of tadalafil in another mouse model of PE, murine reduced uterine perfusion pressure (RUPP) model we have recently developed. METHODS: -At 14.5 dpc we performed RUPP operation in mice to induce PE, administered the animals with tadalafil or vehicle in the drinking water daily from 15.5 dpc, and sacrificed them at 18.5 dpc for analyses. RESULTS: -Tadalafil improved maternal hypertension and glomerular endotheliosis in RUPP mice. Moreover, tadalafil prolonged pregnancy period, and improved survival and growth of the embryos. RUPP increased content of sFlt-1 protein in the placenta, and tadalafil corrected it back to control levels. CONCLUSION: - Tadalafil alleviates PE-like phenotype and FGR in RUPP murine model. RUPP model could help understand the mechanism of how tadalafil works on PE and FGR.
Beneficial effects of nicotinamide on hypertensive mice with impaired endothelial nitric oxide function. International-journal

Phillip K Huynh, Jen Wilder, Sylvia Hiller, John Hagaman, Nobuyuki Takahashi, Nobuyo Maeda-Smithies, Feng Li

Journal of experimental nephrology　1　(1)　1-8　2020

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Nicotinamide (Nam, amide form of niacin acid or nicotinate), a precursor for nicotinamide adenine dinucleotide (NAD+), is important for normal physiological function of organisms. Nam also suppresses mobilization of Ca2+ from sarcoplasmic reticulum into cytoplasm through inhibiting ADP-ribose cyclase. Previously, we have demonstrated that a pharmacological dose of Nam normalizes maternal blood pressure in mouse models of preeclampsia, a pregnancy related hypertensive disorder. We hypothesized that Nam could decrease blood pressure in hypertensive conditions unrelated to pregnancy. Nam at a dose of 500 mg/kg/day was given to wild type (WT) mice treated with L-NAME, endothelial nitric oxide synthase (eNOS)-null and renin transgenic (Renin-Tg) mice via drinking water. Blood pressure was measured by tail-cuff at different stages of treatment. The function and structure of kidneys of WT mice with L-NAME were determined at the end of the study. The gene expression of markers of inflammation and fibrosis in the kidneys of WT mice with L-NAME was also measured. Nam effectively prevented increase in blood pressure in L-NAME treated mice and decreased elevated blood pressure in eNOS-null mice. However, it did not alter high blood pressure in Renin-Tg mice. Nam prevented increase in urinary albumin excretion and collagen deposit in kidneys of WT mice treated with L-NAME. In addition, Nam significantly decreased the mRNA levels of the markers of inflammation and fibrosis in the kidneys of WT mice treated with L-NAME. Nam may execute beneficial effects on hypertensive conditions associated with eNOS dysfunction via suppressing inflammation. Because Nam is generally regarded as safe in humans, it merits further evaluation for the tailored treatment for the subgroup of hypertensive cases associated with impaired eNOS system.
Glomerular Injury Is Exacerbated in Lupus-Prone MRL/lpr Mice Treated with a Protease-Activated Receptor 2 Antagonist.

Rina Itto, Yuji Oe, Kenta Imaruoka, Emiko Sato, Akiyo Sekimoto, Shu Yamakage, Satoshi Kumakura, Hiroshi Sato, Sadayoshi Ito, Nobuyuki Takahashi

The Tohoku journal of experimental medicine　249　(2)　127-133　2019/10

DOI： 10.1620/tjem.249.127 　

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Systemic lupus erythematosus (SLE) is characterized by the production of autoantibodies, which causes multi-organ injury such as lupus nephritis. SLE is associated with hypercoagulability. Activated coagulation factors such as tissue factor and VIIa complex and factor Xa activate protease-activated receptor 2 (PAR2). PAR2 promotes cytokine production through mitogen-activated protein kinase or nuclear factor kappa B signaling, and previous reports demonstrated that inhibition of PAR2 alleviated kidney injuries such as diabetic kidney disease and renal fibrosis in animal models. However, the involvement of PAR2 in the pathogenesis of SLE remains unclear. We therefore administered a selective PAR2 peptide antagonist, FSLLRY-NH2, to SLE-prone 4-month-old MRL-Faslpr mice for 4 weeks. Treatment with FSLLRY-NH2 caused the significant increases in the glomerular mesangial proliferation, glomerular deposition of both immunoglobulin G and complement factor C3d, and glomerular infiltration of Mac2-positive macrophages and CD3-positive T cells, compared with MRL-Faslpr mice treated with saline. In addition, the treatment with the PAR2 antagonist increased renal expression levels of tumor necrosis factor-α (Tnfa) and monocyte chemoattractant protein 1 (Mcp1) mRNA. Collectively, these results suggest that inhibition of PAR2 may increase the severity of inflammation in lupus nephritis; namely, opposite to previous observations, PAR2 has anti-inflammatory properties. We propose that activation of PAR2 could serve as a potential therapeutic option for patients with SLE.
重症妊娠高血圧腎症マウスモデルの開発

橋爪大和, 堰本晃代, 佐藤恵美子, 佐藤博, 高橋信行

日本妊娠高血圧学会雑誌　26　64-64　2019/09
Publisher: (一社)日本妊娠高血圧学会
ISSN： 1880-3172
RUPP-PEモデルマウスを用いた妊娠高血圧腎症に対するタダラフィルの治療効果について

堰本晃代, 橋爪大和, 佐藤恵美子, 田中佳世, 梅川孝, 伊藤貞嘉, 佐藤博, 池田智明, 高橋信行

日本妊娠高血圧学会雑誌　26　66-66　2019/09
Publisher: (一社)日本妊娠高血圧学会
ISSN： 1880-3172
プロテアーゼ活性化受容体2はシスプラチン誘発性腎毒性を悪化させる

渡辺愛理, 大江佑治, 佐藤恵美子, 堰本晃代, 佐藤博, 伊藤貞嘉, 高橋信行

日本腎臓学会誌　61　(3)　284-284　2019/05
Publisher: (一社)日本腎臓学会
ISSN： 0385-2385

eISSN： 1884-0728
ジカルボニルストレスが及ぼす筋細胞への影響

佐藤恵美子, 等々力崇太, 山本多恵, 宮崎真理子, 森建文, 伊藤貞嘉, 佐藤博, 高橋信行

日本腎臓学会誌　61　(3)　312-312　2019/05
Publisher: (一社)日本腎臓学会
ISSN： 0385-2385

eISSN： 1884-0728
Gut microbiome-derived phenyl sulfate contributes to albuminuria in diabetic kidney disease. International-journal

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.
Nicotinamide alleviates kidney injury and pregnancy outcomes in lupus-prone MRL/lpr mice treated with lipopolysaccharide. Peer-reviewed

Imaruoka K, Oe Y, Fushima T, Sato E, Sekimoto A, Sato H, Sugawara J, Ito S, Takahashi N

Biochemical and biophysical research communications　510　(4)　587-593　2019/02
Publisher: Elsevier BV
DOI： 10.1016/j.bbrc.2019.01.110 　

ISSN： 0006-291X
Protease-activated receptor 2 protects against VEGF inhibitor-induced glomerular endothelial and podocyte injury. Peer-reviewed

Oe Y, Fushima T, Sato E, Sekimoto A, Kisu K, Sato H, Sugawara J, Ito S, Takahashi N

Sci Rep　9　(1)　2986　2019
Publisher: Springer Science and Business Media LLC
DOI： 10.1038/s41598-019-39914-8 　

eISSN： 2045-2322
Protease-activated receptor 2 exacerbates cisplatin-induced nephrotoxicity. Peer-reviewed

Watanabe M, Oe Y, Sato E, Sekimoto A, Sato H, Ito S, Takahashi N

American journal of physiology. Renal physiology　316　(4)　F654-F659　2019/01
Publisher: American Physiological Society
DOI： 10.1152/ajprenal.00489.2018 　

ISSN： 1931-857X

eISSN： 1522-1466

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Acute kidney injury (AKI) is associated with hypercoagulability. Tissue factor/factor VIIa complex and factor Xa in the coagulation cascade activate protease-activated receptor 2 (PAR2). Previously, we have shown that PAR2-mediated inflammation aggravates kidney injury in models of diabetic kidney disease and adenine-induced renal fibrosis. However, the role of PAR2 in AKI remains unclear. To clarify the role of PAR2, we administered cisplatin, one of the most common causal factors of AKI, to wild-type and PAR2-deficient mice. The expression levels of tissue factor and PAR2 were significantly increased in the kidneys of mice that were administered cisplatin. A lack of PAR2 corrected the levels of plasma blood urea nitrogen and creatinine as well as ameliorated the acute tubular injury score in the kidney. A lack of PAR2 corrected the infiltration of neutrophils and the gene expression levels of proinflammatory cytokines/chemokines in these mouse kidneys. Similarly, apoptotic markers, such as cleaved caspase-3-positive area and Bax/Bcl2 ratio, were attenuated via PAR2 deletion. Thus, elevated PAR2 exacerbates cisplatin nephrotoxicity, and targeting PAR2 is a novel therapeutic option that aids in the treatment of patients with cisplatin-induced AKI.
Hepatic dysfunction and thrombocytopenia induced by excess sFlt1 in mice lacking endothelial nitric oxide synthase Peer-reviewed

Yuji Oe, Mieko Ko, Tomofumi Fushima, Emiko Sato, S. Ananth Karumanchi, Hiroshi Sato, Junichi Sugawara, Sadayoshi Ito, Nobuyuki Takahashi

Scientific Reports　8　(1)　102　2018/12/01

DOI： 10.1038/s41598-017-18260-7 　

ISSN： 2045-2322
eNOS欠損マウスにおける硝酸ナトリウム(NaNO3)投与の影響

堰本晃代, 成田由紀, 佐藤恵美子, 佐藤博, 伊藤貞嘉, 高橋信行

日本妊娠高血圧学会雑誌　25　112-112　2018/11
Publisher: (一社)日本妊娠高血圧学会
ISSN： 1880-3172
ニコチンアミドは妊娠SLEマウスにおける腎・妊娠予後を改善させる

大江佑治, 伊丸岡健太, 伏間智史, 堰本晃代, 佐藤恵美子, 菅原準一, 佐藤博, 伊藤貞嘉, 高橋信行

日本妊娠高血圧学会雑誌　25　73-73　2018/11
Publisher: (一社)日本妊娠高血圧学会
ISSN： 1880-3172
メタボロミクスによるsFlt-1過剰発現妊娠高血圧腎症モデルでアシルカルニチンが上昇する機序の解明

佐藤恵美子, 金子茉那美, 津國由佳子, 伏間智史, 三枝大輔, 堰本晃代, 伊藤貞嘉, 佐藤博, 高橋信行

日本妊娠高血圧学会雑誌　25　112-112　2018/11
Publisher: (一社)日本妊娠高血圧学会
ISSN： 1880-3172
2年間糖尿病透析予防指導を受けた患者の観察研究

小畑裕史, 宮崎真理子, 佐藤恵美子, 澤田正二郎, 鈴木野の香, 高橋信行, 佐藤博

日本腎臓病薬物療法学会誌　7　(2)　S124-S124　2018/09
Publisher: (一社)日本腎臓病薬物療法学会
ISSN： 2187-0411

eISSN： 2189-8014
eNOS欠損マウスにおける硝酸ナトリウム(NaNO3)投与の影響

堰本晃代, 成田由紀, 佐藤恵美子, 佐藤博, 伊藤貞嘉, 高橋信行

日本高血圧学会総会プログラム・抄録集　41回　OB06-04　2018/09
Publisher: (NPO)日本高血圧学会
ニコチンアミドは妊娠SLEマウスにおける腎・妊娠予後を改善させる

大江佑治, 伊丸岡健太, 伏間智史, 堰本晃代, 佐藤恵美子, 菅原準一, 佐藤博, 伊藤貞嘉, 高橋信行

日本高血圧学会総会プログラム・抄録集　41回　SHRY-03　2018/09
Publisher: (NPO)日本高血圧学会
腎不全マウスの腸内細菌叢と腸内腐敗物の変化とAST-120による影響

佐藤恵美子, 細見晃司, 三枝大輔, 堰本晃代, 國澤純, 丹羽利充, 佐藤博, 高橋信行

JSBMS Letters　43　(Suppl.)　98-98　2018/08
Publisher: (一社)日本医用マススペクトル学会
ISSN： 1881-5464
Relationship between short term variability (STV) and onset of cerebral hemorrhage at ischemia-reperfusion load in fetal growth restricted (FGR) mice Peer-reviewed

Takahiro Minato, Takuya Ito, Yoshiyuki Kasahara, Sayaka Ooshio, Tomofumi Fushima, Akiyo Sekimoto, Nobuyuki Takahashi, Nobuo Yaegashi, Yoshitaka Kimura

Frontiers in Physiology　9　(MAY)　2018/05/18

DOI： 10.3389/fphys.2018.00478 　

ISSN： 1664-042X
血液凝固系に関連した糖尿病性腎症早期診断・薬効マーカー

佐藤恵美子, 大江佑治, 佐藤博, 伊藤貞嘉, 高橋信行

日本腎臓学会誌　60　(3)　402-402　2018/04
Publisher: (一社)日本腎臓学会
ISSN： 0385-2385

eISSN： 1884-0728
sFlt-1過剰発現妊娠高血圧腎症モデルマウスでアシルカルニチンが上昇する機序

佐藤恵美子, 金子茉那美, 津國由佳子, 伏間智史, 三枝大輔, 堰本晃代, 伊藤貞嘉, 佐藤博, 高橋信行

日本腎臓学会誌　60　(3)　334-334　2018/04
Publisher: (一社)日本腎臓学会
ISSN： 0385-2385

eISSN： 1884-0728
Vitamin B3 nicotinamide: A promising candidate for treating preeclampsia and improving fetal growth Peer-reviewed

Nobuyuki Takahashi, Feng Li, Tomofumi Fushima, Gen Oyanagi, Emiko Sato, Yuji Oe, Akiyo Sekimoto, Daisuke Saigusa, Hiroshi Sato, Sadayoshi Ito

Tohoku Journal of Experimental Medicine　244　(3)　243-248　2018/03/01

DOI： 10.1620/tjem.244.243 　

ISSN： 1349-3329 0040-8727
Novel treatment of diabetic kidney disease targeting blood coagulation. Peer-reviewed

Takahashi N, Oe Y

Kidney and Dialysis.　84　(2)　293-296　2018
Impact of the Oral Adsorbent AST-120 on Organ-Specific Accumulation of Uremic Toxins: LC-MS/MS and MS Imaging Techniques 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)　19　2018

DOI： 10.3390/toxins10010019 　

ISSN： 2072-6651
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.
Nrf2 inactivation enhances placental angiogenesis in a preeclampsia mouse model and improves maternal and fetal outcomes. International-journal Peer-reviewed

Masahiro Nezu, Tomokazu Souma, Lei Yu, Hiroki Sekine, Nobuyuki Takahashi, Andrew Zu-Sern Wei, Sadayoshi Ito, Akiyoshi Fukamizu, Zsuzsanna K Zsengeller, Tomohiro Nakamura, Atsushi Hozawa, S Ananth Karumanchi, Norio Suzuki, Masayuki Yamamoto

Science signaling　10　(479)　2017/05/16

DOI： 10.1126/scisignal.aam5711 　

ISSN： 1945-0877
新規全身性エリテマトーデス合併妊娠高血圧腎症モデルマウスの作製

伊丸岡健太, 大江佑治, 佐藤博, 菅原準一, 伊藤貞嘉, 高橋信行

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
Nicotinamide ameliorates a preeclampsia-like condition in mice with reduced uterine perfusion pressure Peer-reviewed

Tomofumi Fushima, Akiyo Sekimoto, Yuji Oe, Emiko Sato, Sadayoshi Ito, Hiroshi Sato, Nobuyuki Takahashi

AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY　312　(2)　F366-F372　2017/02

DOI： 10.1152/ajprenal.00501.2016 　

ISSN： 1931-857X

eISSN： 1522-1466
Hyperactivation of Nrf2 in early tubular development induces nephrogenic diabetes insipidus Peer-reviewed

Takafumi Suzuki, Shiori Seki, Keiichiro Hiramoto, Eriko Naganuma, Eri H. Kobayashi, Ayaka Yamaoka, Liam Baird, Nobuyuki Takahashi, Hiroshi Sato, Masayuki Yamamoto

NATURE COMMUNICATIONS　8　14577　2017/02

DOI： 10.1038/ncomms14577 　

ISSN： 2041-1723
病院レセプトデータを用いた降圧薬の処方動向に関する調査

佐藤倫広, 黒澤桂子, 小原拓, 松浦正樹, 井上隆輔, 高橋信行, 佐藤博, 村井ユリ子, 眞野成康

医療薬学　43　(1)　9-17　2017/01
Publisher: (一社)日本医療薬学会
ISSN： 1346-342X

eISSN： 1882-1499

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レセプトまたは診療支援システムで収集された情報を基に、後ろ向き調査として実施した。外来で降圧薬を処方された35歳以上の高血圧症患者で、2009年3954例、2014年5196例を解析対象者とした。2014年の患者は2009年の患者に比べて心不全および腎障害が有意に高率で、脂質代謝異常症および脳卒中が有意に低率であった。高率に処方されていた降圧薬は、カルシウム拮抗薬およびARBsで、2014年でそれぞれ65.2%、59.9%であった。2009年に比べた2014年における有意な処方割合の増加がアムロジピン、スピロノラクトン、エプレレノン、カルベジロール、ラベタロール、ビソプロロール、およびヒドロクロロチアジドに認め、有意な処方割合の減少がカンデサルタン、ロサルタン、エナラプリル、イミダプリル、アロチノロール、アテノロール、ドキサゾシン、およびブナゾシンに認めた。各種因子補正後、2009年を1.0(基準)とした2014年のアルドステロン拮抗薬、ACE阻害薬、αβ遮断薬、およびα遮断薬処方オッズ比は、それぞれ1.41、0.53、1.77、0.65であった。
Nicotinamide ameliorates a preeclampsia-like condition in mice with reduced uterine perfusion pressure Peer-reviewed

Tomofumi Fushima, Akiyo Sekimoto, Yuji Oe, Emiko Sato, Sadayoshi Ito, Hiroshi Sato, Nobuyuki Takahashi

American Journal of Physiology - Renal Physiology　312　(2)　F366-F372　2017
Publisher: American Physiological Society
DOI： 10.1152/ajprenal.00501.2016 　

ISSN： 1522-1466 0363-6127
Protease-activated receptor 2 exacerbates adenine-induced renal tubulointerstitial injury in mice Peer-reviewed

Sakiko Hayashi, Yuji Oe, Tomofumi Fushima, Emiko Sato, Hiroshi Sato, Sadayoshi Ito, Nobuyuki Takahashi

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS　483　(1)　547-552　2017/01

DOI： 10.1016/j.bbrc.2016.12.108 　

ISSN： 0006-291X

eISSN： 1090-2104
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
Nicotinamide benefits both mothers and pups in two contrasting mouse models of preeclampsia Peer-reviewed

Feng Li, Tomofumi Fushima, Gen Oyanagi, H. W. Davin Townley-Tilson, Emiko Sato, Hironobu Nakada, Yuji Oe, John R. Hagaman, Jennifer Wilder, Manyu Li, Akiyo Sekimoto, Daisuke Saigusa, Hiroshi Sato, Sadayoshi Ito, J. Charles Jennette, Nobuyo Maeda, S. Ananth Karumanchi, Oliver Smithies, Nobuyuki Takahashi

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA　113　(47)　13450-13455　2016/11

DOI： 10.1073/pnas.1614947113 　

ISSN： 0027-8424
妊娠高血圧マウスでは、Nrf2の欠損は、胎盤血管の発育を促し、周産期合併症を改善させる Peer-reviewed

祢津昌広, 相馬友和, 于磊, 伊藤貞嘉, 高橋信行, 鈴木教郎, 山本雅之

日本高血圧学会総会プログラム・抄録集　39回　324-324　2016/09
Publisher: (NPO)日本高血圧学会
METABOLOMIC ANALYSIS OF A MOUSE MODEL OF PREECLAMPSIA INDUCED BY OVERPRODUCING sFLt-1 Peer-reviewed

Sato Emiko, Tsunokuni Yukako, Fushima Tomofumi, Kaneko Manami, Saito Ritsumi, Sekimoto Akiyo, Saigusa Daisuke, Ito Sadayoshi, Sato Hiroshi, Takahashi Nobuyuki

JOURNAL OF HYPERTENSION　34　E69　2016/09

DOI： 10.1097/01.hjh.0000500031.24401.46 　

ISSN： 0263-6352
PIVOTAL ROLE OF HEME OXYGENASE IN AMELIORATION BY NICOTINAMIDE OF FETAL GROWTH RESTRICTION ASSOCIATED WITH PREECLAMPSIA Peer-reviewed

Nakada Hironobu, Fushima Tomofumi, Sekimoto Akiyo, Oe Yuji, Sato Emiko, Ito Sadayoshi, Sato Hiroshi, Takahashi Nobuyuki

JOURNAL OF HYPERTENSION　34　E236　2016/09

DOI： 10.1097/01.hjh.0000500524.43340.2b 　

ISSN： 0263-6352
NOVEL REDUCED UTERINE PERFUSION PRESSURE (RUPP) MODEL OF PREECLAMPSIA IN MICE Peer-reviewed

Fushima Tomofumi, Sekimoto Akiyo, Minato Takahiro, Ito Takuya, Oe Yuji, Kisu Kiyomi, Sato Emiko, Funamoto Kenichi, Kimura Yoshitaka, Ito Sadayoshi, Sato Hiroshi, Takahashi Nobuyuki

JOURNAL OF HYPERTENSION　34　E237　2016/09

DOI： 10.1097/01.hjh.0000500527.66210.66 　

ISSN： 0263-6352
NRF2 DEFICIENCY ALLEVIATES PERINATAL COMPLICATIONS IN PREGNANCY-ASSOCIATED HYPERTENSION MICE VIA ENHANCING PLACENTAL ANGIOGENESIS Peer-reviewed

Nezu Masahiro, Souma Tomokazu, Yu Lei, Sekine Hiroki, Moriguchi Takashi, Takahashi Nobuyuki, Ito Sadayoshi, Suzuki Norio, Yamamoto Masayuki

JOURNAL OF HYPERTENSION　34　E59　2016/09

DOI： 10.1097/01.hjh.0000500005.64305.c1 　

ISSN： 0263-6352
INHIBITING PROTEASE-ACTIVATED RECEPTOR 2 ALLEVIATED PREECLAMPSIA Peer-reviewed

Takahashi Nobuyuki, Ko Mieko, Oe Yuji, Fushima Tomofumi, Sekimoto Akiyo, Sato Emiko, Ito Sadayoshi, Sato Hiroshi

JOURNAL OF HYPERTENSION　34　E101　2016/09

DOI： 10.1097/01.hjh.0000500120.73302.2e 　

ISSN： 0263-6352
MICE LACKING ALDOSTERONE SYNTHASE OR TREATED WITH EPLERENONE ARE RESISTANT TO DIET-INDUCED OBESITY Peer-reviewed

Takahashi Nobuyuki, Uchida Taeko, Iwai Toshiki, Sekimoto Akiyo, Sato Hiroshi

JOURNAL OF HYPERTENSION　34　E137　2016/09

DOI： 10.1097/01.hjh.0000500249.60294.b8 　

ISSN： 0263-6352
APPLICATION OF NOVEL REDUCED UTERINE PERFUSION PRESSURE (RUPP) MODEL OF PREECLAMPSIA IN C57BL/6J MICE Peer-reviewed

Sekimoto Akiyo, Fushima Tomofumi, Oe Yuji, Kisu Kiyomi, Sato Emiko, Ito Sadayoshi, Sato Hiroshi, Takahashi Nobuyuki

JOURNAL OF HYPERTENSION　34　E409　2016/09

DOI： 10.1097/01.hjh.0000501052.07978.d5 　

ISSN： 0263-6352
AN ORAL FACTOR XA INHIBITOR, EDOXABAN, ALLEVIATES DIABETIC NEPHROPATHY IN MICE LACKING eNOS Peer-reviewed

Oe Yuji, Fushima Tomofumi, Sato Emiko, Sato Hiroshi, Ito Sadayoshi, Takahashi Nobuyuki

JOURNAL OF HYPERTENSION　34　E102　2016/09

DOI： 10.1097/01.hjh.0000500125.77396.fa 　

ISSN： 0263-6352
IGA NEPHROPATHY IS EXACERBATED BY PREGNANCY AND IS A RISK FACTOR FOR PREECLAMPSIA IN GROUPED DDY MICE Peer-reviewed

Fushima Tomofumi, Oe Yuji, Sato Emiko, Suzuki Yusuke, Tomino Yasuhiko, Ito Sadayoshi, Sato Hiroshi, Takahashi Nobuyuki

JOURNAL OF HYPERTENSION　34　E427　2016/09

DOI： 10.1097/01.hjh.0000501101.72126.01 　

ISSN： 0263-6352
PAR2 SIGNALING EXACERBATES DIABETIC NEPHROPATHY Peer-reviewed

Oe Yuji, Hayashi Sakiko, Fushima Tomofumi, Sato Emiko, Kisu Kiyomi, Sato Hiroshi, Ito Sadayoshi, Takahashi Nobuyuki

JOURNAL OF HYPERTENSION　34　E326　2016/09

DOI： 10.1097/01.hjh.0000500812.17722.74 　

ISSN： 0263-6352
NICOTINAMIDE DECREASES BP IN MICE BY TWO MECHANISMS Peer-reviewed

Fushima Tomofumi, Sekimoto Akiyo, Ishida Akinori, Nakada Hironobu, Sato Hiroshi, Ito Sadayoshi, Takahashi Nobuyuki

JOURNAL OF HYPERTENSION　34　E98-E99　2016/09

DOI： 10.1097/01.hjh.0000500111.89442.d5 　

ISSN： 0263-6352
Coagulation Factor Xa and Protease-Activated Receptor 2 as Novel Therapeutic Targets for Diabetic Nephropathy Peer-reviewed

Yuji Oe, Sakiko Hayashi, Tomofumi Fushima, Emiko Sato, Kiyomi Kisu, Hiroshi Sato, Sadayoshi Ito, Nobuyuki Takahashi

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY　36　(8)　1525-1533　2016/08

DOI： 10.1161/ATVBAHA.116.307883 　

ISSN： 1079-5642

eISSN： 1524-4636
Reduced Uterine Perfusion Pressure (RUPP) Model of Preeclampsia in Mice Peer-reviewed

Tomofumi Fushima, Akiyo Sekimoto, Takahiro Minato, Takuya Ito, Yuji Oe, Kiyomi Kisu, Emiko Sato, Kenichi Funamoto, Toshiyuki Hayase, Yoshitaka Kimura, Sadayoshi Ito, Hiroshi Sato, Nobuyuki Takahashi

PLOS ONE　11　(5)　e0155426　2016/05

DOI： 10.1371/journal.pone.0155426 　

ISSN： 1932-6203
A novel and sensitive assay for heme oxygenase activity Peer-reviewed

Saki Iwamori, Emiko Sato, Daisuke Saigusa, Kouichi Yoshinari, Sadayoshi Ito, Hiroshi Sato, Nobuyuki Takahashi

AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY　309　(7)　F667-F671　2015/10

DOI： 10.1152/ajprenal.00210.2015 　

ISSN： 1931-857X

eISSN： 1522-1466
A novel and sensitive assay for heme oxygenase activity Peer-reviewed

Saki Iwamori, Emiko Sato, Daisuke Saigusa, Kouichi Yoshinari, Sadayoshi Ito, Hiroshi Sato, Nobuyuki Takahashi

American Journal of Physiology - Renal Physiology　309　(7)　F667-F671　2015/09/01
Publisher: American Physiological Society
DOI： 10.1152/ajprenal.00210.2015 　

ISSN： 1522-1466 0363-6127
A Survey of Self-medication Practices and Related Factors in the General Population: the Ohasama Study Peer-reviewed

Michihiro Satoh, Akihiro Matsumoto, Azusa Hara, Saki Iwamori, Taku Obara, Masahiro Kikuya, Hirohito Metoki, Miki Hosaka, Kei Asayama, Nobuyuki Takahashi, Hiroshi Sato, Nariyasu Mano, Yutaka Imai, Takayoshi Ohkubo

YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN　134　(12)　1347-1355　2014/12

DOI： 10.1248/yakushi.14-00179 　

ISSN： 0031-6903
THE ROLE OF COAGULATION FACTOR XA AND PROTEASE ACTIVATED RECEPTORS IN DIABETIC NEPHROPATHY Peer-reviewed

Oe Yuji, Sato Hiroshi, Ito Sadayoshi, Takahashi Nobuyuki

NEPHROLOGY　19　88-89　2014/05

ISSN： 1320-5358

eISSN： 1440-1797
THERAPEUTIC EFFECT OF NICOTINAMIDE ON IgA NEPHROPATHY Peer-reviewed

Fushima Tomofumi, Oe Yuji, Iwamori Saki, Sato Emiko, Suzuki Yusuke, Tomino Yasuhiko, Ito Sadayoshi, Sato Hiroshi, Takahashi Nobuyuki

NEPHROLOGY　19　146-146　2014/05

ISSN： 1320-5358

eISSN： 1440-1797
A NOVEL AND SENSITIVE ASSAY OF KIDNEY HEME OXYGENASE ACTIVITY Peer-reviewed

Iwamori Saki, Sato Emiko, Yoshinari Kouichi, Mano Nariyasu, Ito Sadayoshi, Sato Hiroshi, Takahashi Nobuyuki

NEPHROLOGY　19　185-185　2014/05

ISSN： 1320-5358

eISSN： 1440-1797
Pathology of glomerular lipidosis Peer-reviewed

Hiroshi Sato, Nobuyuki Takahashi, Emiko Sato, Kiyomi Kisu, Sadayoshi Ito, Takao Saito

CLINICAL AND EXPERIMENTAL NEPHROLOGY　18　(2)　194-196　2014/04

DOI： 10.1007/s10157-013-0882-9 　

ISSN： 1342-1751

eISSN： 1437-7799
Bartter syndrome, Gitelman syndrome, Liddle syndrome. Peer-reviewed

Takahashi N, Ito S

Kidney diseases/hemodialysis updates.　217-219　2014
Cardiac natriuretic peptides act via p38 MAPK to induce the brown fat thermogenic program in mouse and human adipocytes (vol 122, pg 1022, 2012) Peer-reviewed

Marica Bordicchia, Dianxin Liu, Ez-Zoubir Amri, Gerard Ailhaud, Paolo Dessi-Fulgheri, Chaoying Zhang, Nobuyuki Takahashi, Riccardo Sarzani, Sheila Collins

JOURNAL OF CLINICAL INVESTIGATION　122　(4)　1584-1584　2012/04

DOI： 10.1172/JCI63775 　

ISSN： 0021-9738
eNOS Deficiency Acts through Endothelin to Aggravate sFlt-1-Induced Pre-Eclampsia-Like Phenotype Peer-reviewed

Feng Li, John R. Hagaman, Hyung-Suk Kim, Nobuyo Maeda, J. Charles Jennette, James E. Faber, S. Ananth Karumanchi, Oliver Smithies, Nobuyuki Takahashi

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY　23　(4)　652-660　2012/04

DOI： 10.1681/ASN.2011040369 　

ISSN： 1046-6673
Cardiac natriuretic peptides act via p38 MAPK to induce the brown fat thermogenic program in mouse and human adipocytes Peer-reviewed

Marica Bordicchia, Dianxin Liu, Ez-Zoubir Amri, Gerard Ailhaud, Paolo Dessi-Fulgheri, Chaoying Zhang, Nobuyuki Takahashi, Riccardo Sarzani, Sheila Collins

JOURNAL OF CLINICAL INVESTIGATION　122　(3)　1022-1036　2012/03

DOI： 10.1172/JCI59701 　

ISSN： 0021-9738

eISSN： 1558-8238
Evaluation of pre-hospital clinical training in advanced pharmacy education in Japan. Peer-reviewed

Hashimoto T, Ohkubo T, Takahashi N, Murai Y, Sato K, Terata S, Metoki H, Kikuya M, Hirasawa N, Tomioka Y, Oba M, Imai Y, Sato H

Jpn J Pharm Health Care Sci.　38　322-331　2012
eNOS and diabetic nephropathy. Peer-reviewed

Li F, Takahashi N

J Nephrol Therapeutic.　10　S2-004　2012
Cardiac Natriuretic Peptides as Cardiometabolic Hormones: ANP and BNP Induce Lipolysis, Mitochondriogenesis, and Uncoupled Respiration via cGMP/PKG and P38 MAPK in Human Adipocytes Peer-reviewed

Marica Bordicchia, Dianxin Liu, Ez-Zoubir Amri, Gerard Ailhaud, Nobuyuki Takahashi, Paolo Dessi-Fulgheri, Riccardo Sarzani, Sheila Collins

HYPERTENSION　58　(5)　E166-E166　2011/11

ISSN： 0194-911X
A modest decrease in endothelial NOS in mice comparable to that associated with human NOS3 variants exacerbates diabetic nephropathy Peer-reviewed

Chih-Hong Wang, Feng Li, Sylvia Hiller, Hyung-Suk Kim, Nobuyo Maeda, Oliver Smithies, Nobuyuki Takahashi

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA　108　(5)　2070-2075　2011/02

DOI： 10.1073/pnas.1018766108 　

ISSN： 0027-8424
A modest decrease in endothelial NOS in mice comparable to that associated with human NOS3 variants exacerbates diabetic nephropathy (vol 108, pg 2070, 2011) Peer-reviewed

Chih-Hong Wang, Feng Li, Sylvia Hiller, Hyung-Suk Kim, Nobuyo Maeda, Oliver Smithies, Nobuyuki Takahashi

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA　108　(8)　3453-3453　2011/02

DOI： 10.1073/pnas.1101346108 　

ISSN： 0027-8424
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
Common variants in the ATP2B1 gene are associated with susceptibility to hypertension: the Japanese Millennium Genome Project. Peer-reviewed

Tabara Y, Kohara K, Kita Y, Hirawa N, Katsuya T, Ohkubo T, Hiura Y, Tajima A, Morisaki T, Miyata T, Nakayama T, Takashima N, Nakura J, Kawamoto R, Takahashi N, Hata A, Soma M, Imai Y, Kokubo Y, Okamura T, Tomoike H, Iwai N, Ogihara T, Inoue I, Tokunaga K, Johnson T, Caulfield M, Munroe P, Global Blood, Pressure Genetics Consortium, Umemura S, Ueshima H, Miki T

Hypertension　56　(5)　973-980　2010/11

DOI： 10.1161/HYPERTENSIONAHA.110.153429 　

ISSN： 0194-911X
Elevated tissue factor expression contributes to exacerbated diabetic nephropathy in mice lacking eNOS fed a high fat diet Peer-reviewed

F. Li, C. -H. Wang, J. -G. Wang, T. Thai, G. Boysen, L. Xu, A. L. Turner, A. S. Wolberg, N. Mackman, N. Maeda, N. Takahashi

JOURNAL OF THROMBOSIS AND HAEMOSTASIS　8　(10)　2122-2132　2010/10

DOI： 10.1111/j.1538-7836.2010.03976.x 　

ISSN： 1538-7933
Loss of Bradykinin Signaling Does Not Accelerate the Development of Cardiac Dysfunction in Type 1 Diabetic Akita Mice Peer-reviewed

Adam R. Wende, Jamie Soto, Curtis D. Olsen, Karla M. P. Pires, John C. Schell, Frederic Larrieu-Lahargue, Sheldon E. Litwin, Masao Kakoki, Nobuyuki Takahashi, Oliver Smithies, E. Dale Abel

ENDOCRINOLOGY　151　(8)　3536-3542　2010/08

DOI： 10.1210/en.2010-0256 　

ISSN： 0013-7227
The renin angiotensin system and metabolic syndrome. Peer-reviewed

Wang C-H. Li F, Takahashi N

Open Hypertens J.　3　1-13　2010
Cardiac Contractility and Mitochondrial Function Following Genetic Deletion of Bradykinin Receptors B1 and B2 in Type 1 Diabetic Akita Mice. Peer-reviewed

Wende AR, Soto J, Olsen CD, Pires KMP, Schell JC, Litwin SE, Kakoki M, Takahashi N, Smithies O, Abel ED

Endocrinology.　151　3536-3546　2010
The renin angiotensin system and the metabolic syndrome. Peer-reviewed

Wang CH, Li F, Takahashi N

The open hypertension journal　3　1-13　2010

DOI： 10.2174/1876526203010001 　
Mouse Models of Diabetic Nephropathy Peer-reviewed

Frank C. Brosius, Charles E. Alpers, Erwin P. Bottinger, Matthew D. Breyer, Thomas M. Coffman, Susan B. Gurley, Raymond C. Harris, Masao Kakoki, Matthias Kretzler, Edward H. Leiter, Moshe Levi, Richard A. McIndoe, Kumar Sharma, Oliver Smithies, Katalin Susztak, Nobuyuki Takahashi, Takamune Takahashi

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY　20　(12)　2503-2512　2009/12

DOI： 10.1681/ASN.2009070721 　

ISSN： 1046-6673
Inhibition of Pancreatic Lipase and the Renin Angiotensin System Synergistically Decreases Body Fat Peer-reviewed

Feng Li, Nobuyuki Takahashi

CIRCULATION　120　(18)　S1112-S1112　2009/11

ISSN： 0009-7322
Impact of Bradykinin Receptor Deficiency on Cardiac Contractility and Mitochondrial Function in Type 1 Diabetic Akita Mice Peer-reviewed

Adam R. Wende, Jamie Soto, John C. Schell, Curtis D. Olsen, Sheldon E. Litwin, Masao Kakoki, Nobuyuki Takahashi, Oliver Smithles, E. Dale Abel

DIABETES　58　A338-A338　2009/06

ISSN： 0012-1797
Association of TNFRSF4 gene polymorphisms with essential hypertension. International-journal Peer-reviewed

Mashimo Y, Suzuki Y, Hatori K, Tabara Y, Miki T, Tokunaga K, Katsuya T, Ogihara T, Yamada M, Takahashi N, Makita Y, Nakayama T, Soma M, Hirawa N, Umemura S, Ohkubo T, Imai Y, Hata A

Journal of hypertension　26　(5)　902-913　2008/05

DOI： 10.1097/HJH.0b013e3282f6a65e 　

ISSN： 0263-6352
Increased energy expenditure, dietary fat wasting, and resistance to diet-induced obesity in mice lacking renin Peer-reviewed

Nobuyuki Takahashi, Feng Li, Kunjie Hua, Jianbei Deng, Chih-Hong Wang, Robert R. Bowers, Timothy J. Bartness, Hyung-Suk Kim, Joyce B. Harp

CELL METABOLISM　6　(6)　506-512　2007/12

DOI： 10.1016/j.cmet.2007.10.011 　

ISSN： 1550-4131
Early cardiac hypertrophy in mice with impaired calmodulin regulation of cardiac muscle Ca2+ release channel Peer-reviewed

Naohiro Yamaguchi, Nobuyuki Takahashi, Le Xu, Oliver Smithies, Gerhard Meissner

JOURNAL OF CLINICAL INVESTIGATION　117　(5)　1344-1353　2007/05

DOI： 10.1172/JCI29515 　

ISSN： 0021-9738
Tandem mass spectrometry measurements of creatinine in mouse plasma and urine for determining glomerular filtration rate Peer-reviewed

N. Takahashi, G. Boysen, F. Li, Y. Li, J. A. Swenberg

KIDNEY INTERNATIONAL　71　(3)　266-271　2007/02

DOI： 10.1038/sj.ki.5002033 　

ISSN： 0085-2538
Measurement of creatinine in mouse plasma and urine for determining GFR using tandem mass spectrometry. Peer-reviewed

Takahashi N, Boysen G, Li Y, Li F, Swenberg JA

Kidney Int.　71　266-271　2007
Absence of renin stimulates fatty acid oxidation and decreases fat absorption Peer-reviewed

Nobuyuki Takahashi, Feng Li, Kunjie Hua, Jianbei Deng, Hyung-Suk Kim, Joyce B. Harp

JOURNAL OF HYPERTENSION　24　86-86　2006/12

ISSN： 0263-6352
Senescence-associated phenotypes in Akita diabetic mice are enhanced by absence of bradykinin B2 receptors Peer-reviewed

M Kakoki, CM Kizer, XW Yi, N Takahashi, HS Kim, CR Bagnell, CJS Edgell, N Maeda, JC Jennette, O Smithies

JOURNAL OF CLINICAL INVESTIGATION　116　(5)　1302-1309　2006/05

DOI： 10.1172/JCI26958 　

ISSN： 0021-9738
Protein inhibitor of activated STAT3 inhibits adipogenic gene expression Peer-reviewed

JB Deng, KJ Hua, EJ Caveney, N Takahashi, JB Harp

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS　339　(3)　923-931　2006/01

DOI： 10.1016/j.bbrc.2005.10.217 　

ISSN： 0006-291X
Kidney function in mice lacking aldosterone Peer-reviewed

N Makhanova, G Lee, N Takahashi, MLS Lopez, RA Gomez, HS Kim, O Smithies

AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY　290　(1)　F61-F69　2006/01

DOI： 10.1152/ajprenal.00257.2005 　

ISSN： 1931-857X
Role of natriuretic peptide receptor guanylyl cyclase-A in myocardial infarction evaluated using genetically engineered mice Peer-reviewed

M. Nakanishi, Y. Saito, I. Kishimoto, M. Harada, K. Kuwahara, N. Takahashi, R. Kawakami, Y. Nakagawa, K. Tanimoto, S. Yasuno, S. Usami, Y. Li, Y. Adachi, A. Fukamizu, D.L. Garbers, K. Nakao

Hypertension　46　(2)　441-447　2005/08

DOI： 10.1161/01.HYP.0000173420.31354.ef 　
Increased susceptibility to heart failure in response to volume overload in mice lacking natriuretic peptide receptor-A gene Peer-reviewed

T Nishikimi, Hagaman, JR, N Takahashi, HS Kim, H Matsuoka, O Smithies, N Maeda

CARDIOVASCULAR RESEARCH　66　(1)　94-103　2005/04

DOI： 10.1016/j.cardiores.2004.12.014 　

ISSN： 0008-6363
Ren1c homozygous null mice are hypotensive and polyuric, but heterozygotes are indistinguishable from wild-type Peer-reviewed

N Takahashi, MLSS Lopez, JE Cowhig, MA Taylor, T Hatada, E Riggs, G Lee, RA Gomez, HS Kim, O Smithies

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY　16　(1)　125-132　2005/01

DOI： 10.1681/ASN.2004060490 　

ISSN： 1046-6673
Diabetic nephropathy is markedly enhanced in mice lacking the bradykinin B2 receptor Peer-reviewed

M Kakoki, N Takahashi, JC Jennette, O Smithies

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA　101　(36)　13302-13305　2004/09

DOI： 10.1073/pnat.0405449101 　

ISSN： 0027-8424
Hypertension and abnormal fat distribution but not insulin resistance in mice with P465L PPAR gamma Peer-reviewed

YS Tsai, HJ Kim, N Takahashi, HS Kim, Hagaman, JR, JK Kim, N Maeda

JOURNAL OF CLINICAL INVESTIGATION　114　(2)　240-249　2004/07

DOI： 10.1172/JCI200420964 　

ISSN： 0021-9738
Altering the expression in mice of genes by modifying their 3 ' regions Peer-reviewed

M Kakoki, YS Tsai, HS Kim, S Hatada, DJ Ciavatta, N Takahashi, LW Arnold, N Maeda, O Smithies

DEVELOPMENTAL CELL　6　(4)　597-606　2004/04

DOI： 10.1016/S1534-5807(04)00094-2 　

ISSN： 1534-5807
Human genetics, animal models and computer simulations for studying hypertension Peer-reviewed

N Takahashi, O Smithies

TRENDS IN GENETICS　20　(3)　136-145　2004/03

ISSN： 0168-9525
Minireview: Computer simulations of blood pressure regulation by the renin-angiotensin system Peer-reviewed

N Takahashi, Hagaman, JR, HS Kim, O Smithies

ENDOCRINOLOGY　144　(6)　2184-2190　2003/06

DOI： 10.1210/en.2002-221045 　

ISSN： 0013-7227
Posttranscriptional compensation for heterozygous disruption of the kidney-specific NaK2Cl cotransporter gene Peer-reviewed

N Takahashi, HL Brooks, JB Wade, W Liu, Y Kondo, S Ito, MA Knepper, O Smithies

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY　13　(3)　604-610　2002/03

ISSN： 1046-6673
Importance of quantitative genetic variations in the etiology of hypertension Peer-reviewed

O Smithies, HS Kim, N Takahashi, MH Edgell

KIDNEY INTERNATIONAL　58　(6)　2265-2280　2000/12

ISSN： 0085-2538
Uncompensated polyuria in a mouse model of Bartter's syndrome Peer-reviewed

N Takahashi, DR Chernavvsky, RA Gomez, P Igarashi, HJ Gitelman, O Smithies

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA　97　(10)　5434-5439　2000/05

ISSN： 0027-8424
Loss of function by a mutation in thiazide-sensitive Na-Cl cotranspoter gene found in Gitelman's syndrome

Y Taniyama, K Takeuchi, N Takahashi, A Sugawara, Y Ikeda, K Sato, S Ito

CONTROL AND DISEASES OF SODIUM DEPENDENT TRANSPORT PROTEINS AND ION CHANNELS　1208　55-56　2000

ISSN： 0531-5131
Transcriptional suppression of rat angiotensin AT1a receptor gene expression by interferon-gamma in vascular smooth muscle cells Peer-reviewed

Y Ikeda, K Takeuchi, T Kato, Y Taniyama, K Sato, N Takahashi, A Sugawara, S Ito

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS　262　(2)　494-498　1999/08

DOI： 10.1006/bbrc.1999.1226 　

ISSN： 0006-291X
Gene targeting approaches to analyzing hypertension Peer-reviewed

N Takahashi, O Smithies

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY　10　(7)　1598-1605　1999/07

ISSN： 1046-6673
The natriuretic peptide clearance receptor locally modulates the physiological effects of the natriuretic peptide system Peer-reviewed

N Matsukawa, WJ Grzesik, N Takahashi, KN Pandey, S Pang, M Yamauchi, O Smithies

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA　96　(13)　7403-7408　1999/06

ISSN： 0027-8424
ヒトサイアザイド感受性Na-Cl共輸送体（hTSC）機能発現系の確立とこれを用いた構造機能連関の検討 Peer-reviewed

谷山佳弘, 竹内和久, 菅原明, 池田勧夫, 加藤太郎, 高橋信行, 伊藤貞嘉

セラピューティック・リサーチ　20　(5)　1364-1367　1999
ヒトサイアザイド感受性Na-Cl共輸送体(hTSC)機能発現系の確立とこれを用いた構造機能関連の検討

谷山佳弘, 竹内和久, 菅原明, 池田勧夫, 加藤太郎, 高橋信行, 伊藤貞嘉

Therapeutic Research　20　(5)　134-137　1999
Structure and transcriptional function of the 5 '-flanking region of rat thromboxane receptor gene Peer-reviewed

N Takahashi, K Takeuchi, A Sugawara, Y Taniyama, T Kato, CS Wilcox, K Abe, S Ito

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS　244　(2)　489-493　1998/03

ISSN： 0006-291X
IL-6によるラット・トロンボキサン受容体遺伝子の発現調節 Peer-reviewed

谷山佳弘, 竹内和久, 高橋信行, 菅原明, 加藤太郎, 阿部倫明, 阿部圭志, 伊藤貞嘉

血圧　5　(3)　250-254　1998
プロスタグランジン受容体 Peer-reviewed

竹内和久, 谷山佳弘, 高橋信行, 伊藤貞嘉

セラピューティック・リサーチ　19　(5)　1565-1568　1998
Three cases of Gitelman's syndrome possibly caused by different mutations in the thiazide-sensitive Na-Cl cotransporter Peer-reviewed

K Takeuchi, T Kato, Y Taniyama, K Tsunoda, N Takahashi, Y Ikeda, K Omata, Y Imai, T Saito, S Ito, K Abe

INTERNAL MEDICINE　36　(8)　582-585　1997/08

ISSN： 0918-2918
Retinoid X receptors in the kidney: Their protein expression and functional significance Peer-reviewed

A Sugawara, N Sanno, N Takahashi, RY Osamura, K Abe

ENDOCRINOLOGY　138　(8)　3175-3180　1997/08

ISSN： 0013-7227
Rat kidney thromboxane synthase: cDNA cloning and gene expression regulation in hydronephrotic kidney Peer-reviewed

E Tsutsumi, K Takeuchi, T Abe, N Takahashi, T Kato, Y Taniyama, Y Ikeda, S Ito, K Abe

PROSTAGLANDINS　53　(6)　423-431　1997/06

ISSN： 0090-6980
Tyrosine kinase, phosphatidylinositol 3-kinase, and protein kinase C regulate insulin-stimulated NaCl absorption in the thick ascending limb Peer-reviewed

O Ito, Y Kondo, M Oba, N Takahashi, K Omata, K Abe

KIDNEY INTERNATIONAL　51　(4)　1037-1041　1997/04

ISSN： 0085-2538
Assignment of rat thromboxane synthase gene (Tbxas) to chromosome 4q21->q22 by fluorescence in situ hybridization Peer-reviewed

K Takeuchi, E Tsutsumi, T Abe, N Takahashi, T Kato, Y Taniyama, Y Ikeda, K Abe

CYTOGENETICS AND CELL GENETICS　76　(1-2)　47-48　1997

ISSN： 0301-0171
Association of a mutation in thiazide-sensitive Na-Cl cotransporter with familial Gitelman's syndrome Peer-reviewed

K Takeuchi, S Kure, T Kato, Y Taniyama, N Takahashi, Y Ikeda, T Abe, K Narisawa, Y Muramatsu, K Abe

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM　81　(12)　4496-4499　1996/12

ISSN： 0021-972X

eISSN： 1945-7197
Immunolocalization of rat thromboxane receptor in the kidney Peer-reviewed

N Takahashi, K Takeuchi, T Abe, A Sugawara, K Abe

ENDOCRINOLOGY　137　(11)　5170-5173　1996/11

ISSN： 0013-7227

eISSN： 1945-7170
Functional analysis and chromosomal gene assignment of rat kidney prostaglandin EP3 receptor. International-journal Peer-reviewed

K Takeuchi, N Takahashi, T Kato, T Abe, Y Taniyama, E Tsutsumi, O Ito, K Nakagawara, K Abe

Kidney International. Supplement　55　S183-6　1996/06

ISSN： 0098-6577

More details Close

We have reported two isoformes of rat prostaglandin EP3 receptor with their different carboxyl-terminal tails (rEP3A and rEP3B receptors), which are derived by alternative RNA splicing, and both receptors have been shown to be localized to renal distal tubules. In the present study, we characterized the signal transduction system of rat kidney EP3 receptors either in a renal cell line mimicking renal distal tubule cells, TKC2, or in COS-7 cells by functional expression of these receptors. We also examined the chromosomal localization of the EP3 receptor gene by fluorescence in situ hybridization (FISH). In TKC2 cells, vasopressin (AVP, 10(-7) M), prostaglandin (PG) E2 (10(-7) M), or forskolin (10(-8) M) markedly stimulated cyclic AMP formation. Overexpression of the rEP3A receptor significantly attenuated the AVP-, PGE2- or forskolin-induced cyclic AMP formation, whereas there was no change with rEP3B receptor expression. On the other hand, in COS-7 cells transfected with rEP3A receptor cDNA, PGE2 (10(-7) M) did not affect cytosolic free calcium concentration ([Ca2+]i), whereas transfection of rEP3B receptor cDNA evoked PGE2-induced increases in [Ca2+]i. Moreover, we have revealed that the rEP3 receptor gene is localized to rat chromosome 2q44-45. In conclusion, rEP3A or rEP3B receptor is suggested as a mediator of the natriuretic/diuretic action of PGE2 in renal distal tubules via a decrease in cyclic AMP formation or an increase in [Ca2+]i, respectively. Information of the gene assignment of rat EP3 receptor to rat chromosome 2q44-45 is useful for further analysis of the role of EP3 receptor in genetically hypertensive rat models.
Tubular effects of insulin. International-journal Peer-reviewed

N Takahashi, O Ito, K Abe

Hypertension research : official journal of the Japanese Society of Hypertension　19 Suppl 1　(Suppl1)　S41-5-S45　1996/06

ISSN： 0916-9636

More details Close

The direct effect of insulin on NaCl transport in proximal tubules and thick ascending limbs of Henle's loop were examined. First, the effects of insulin on intracellular pH (pHi) in the in vitro microperfused rabbit S2 proximal straight tubules (PST) were examined using a fluorescent technique. Addition of insulin to the bath increased pHi in a dose-dependent manner at concentrations ranging from 10(-11) to 10(-6) mol/l, and its ED50 was 10(-9) mol/l. The insulin-induced pHi increase was almost completely inhibited by 10(-3) mol/l amiloride in the lumen, indicating that insulin activates luminal Na/H exchange in PST. Next, the effect of insulin on the transepithelial voltage (Vt) and lumen-to-bath Cl flux (JCl) were examined in the in vitro microperfused rabbit medullary thick ascending limbs of Henle's loop (MTAL). Insulin in the bath increased Vt in a dose-dependent manner, and its ED50 was 5 X 10(-9) mol/l. Insulin significantly increased JCl. The insulin-mediated increase in Vt was abolished by ouabain and furosemide. Dibutyryl-cAMP (dbcAMP) increased Vt and JCl. H-8 abolished the effect of dbcAMP, while it did not inhibit the actions of insulin. Removal of extracellular Ca did not affect the effects of insulin on Vt and JCl. Chelation of intracellular Ca with BAPTA/AM inhibited the actions of insulin without affecting basal values. Calmodulin (CaM) inhibitors, trifluoperazine and W-7, inhibited the actions of insulin more than 90%. These results indicate that insulin directly increases NaCl reabsorption in the MTAL, which requires the activation of Ca-CaM system, independent of the adenylate cyclase-cAMP-PKA system. In conclusion, insulin directly stimulates NaCl reabsorption in the in vitro microperfused rabbit PST and MTAL.
Functional analysis and chromosomal gene assignment of rat kidney prostaglandin EP(3) receptor Peer-reviewed

K Takeuchi, N Takahashi, T Kato, T Abe, Y Taniyama, E Tsutsumi, O Ito, KI Nakagawara, K Abe

KIDNEY INTERNATIONAL　55　S183-S186　1996/06

ISSN： 0085-2538
Intrarenal mRNA expression of the rat MDCK-type chloride channel Peer-reviewed

T Abe, K Takeuchi, N Takahashi, Y Taniyama, E Tsutsumi, K Abe

NEPHRON　73　(1)　23-26　1996/05

ISSN： 0028-2766
Assignment of the gene for rat thromboxane receptor (Tbxa2r) to chromosome 7q11 by fluorescence in situ hybridization Peer-reviewed

K. Takeuchi, K. Nakagawara, M. Mori, T. Abe, N. Takahashi, E. Tsutsumi, Y. Taniyama, T. Kato, T. Takeuchi, K. Abe

Cytogenetic and Genome Research　73　(1-2)　79-80　1996/01/01

DOI： 10.1159/000134312 　

ISSN： 1424-859X 1424-8581
Intrarenal mRNA Expression of the rat mdck-type chloride channel Peer-reviewed

Takaaki Abe, Kazuhisa Takeucbi, Nobuyuki Takahashi, Yoshiyuki Taniyama, Eikatsu Tsutsumi, Keishi Abe

Nephron　73　(1)　23-26　1996

DOI： 10.1159/000188993 　

ISSN： 2235-3186 1660-8151
20-hydroxyeicosatetraenoic Acidの血管収縮作用とその作用機序

内海由也, 尾股健, 許士郎, 有馬秀二, 伊藤修, 高橋信行, 佐藤龍行, 清水哲, 堤栄克, 山田雅昭, 阿部文明, 伊藤貞嘉, 阿部圭志

脈管学　36　167-173　1996
Assignment of the gene for rat thromboxane receptor (Tbxa2r) to chromosome 7q11 by fluorescence in situ hybridization Peer-reviewed

K Takeuchi, K Nakagawara, M Mori, T Abe, N Takahashi, E Tsutsumi, Y Taniyama, T Kato, T Takeuchi, K Abe

CYTOGENETICS AND CELL GENETICS　73　(1-2)　79-80　1996

ISSN： 0301-0171
IMMUNOHISTOCHEMICAL LOCALIZATION OF THROMBOXANE RECEPTOR AND THROMBOXANE SYNTHASE IN RAT TESTIS Peer-reviewed

N TAKAHASHI, K TAKEUCHI, T ABE, K MURAKAMI, M YAMAGUCHI, K ABE

ENDOCRINOLOGY　136　(9)　4143-4146　1995/09

ISSN： 0013-7227

eISSN： 1945-7170
ROLE OF CALCIUM IN INSULIN-STIMULATED NACL TRANSPORT IN MEDULLARY THICK ASCENDING LIMB Peer-reviewed

O ITO, Y KONDO, N TAKAHASHI, K OMATA, K ABE

AMERICAN JOURNAL OF PHYSIOLOGY-RENAL FLUID AND ELECTROLYTE PHYSIOLOGY　269　(2)　F236-F241　1995/08

ISSN： 0363-6127
RAT KIDNEY THROMBOXANE RECEPTOR - MOLECULAR-CLONING, SIGNAL-TRANSDUCTION, AND INTRARENAL EXPRESSION LOCALIZATION Peer-reviewed

T ABE, K TAKEUCHI, N TAKAHASHI, E TSUTSUMI, Y TANIYAMA, K ABE

JOURNAL OF CLINICAL INVESTIGATION　96　(2)　657-664　1995/08

ISSN： 0021-9738
CYTOSOLIC CA2+ DYNAMICS IN HAMSTER ASCENDING THIN LIMB OF HENLES LOOP Peer-reviewed

N TAKAHASHI, Y KONDO, O ITO, Y IGARASHI, K OMATA, K ABE

AMERICAN JOURNAL OF PHYSIOLOGY-RENAL FLUID AND ELECTROLYTE PHYSIOLOGY　268　(6)　F1148-F1153　1995/06

ISSN： 0363-6127
VASOPRESSIN STIMULATES CL- TRANSPORT IN ASCENDING THIN LIMB OF HENLES LOOP IN HAMSTER Peer-reviewed

N TAKAHASHI, Y KONDO, O ITO, Y IGARASHI, K OMATA, K ABE

JOURNAL OF CLINICAL INVESTIGATION　95　(4)　1623-1627　1995/04

ISSN： 0021-9738
Amiloride-sensitive Na+/H+ antiporter in basolateral membrane of hamster ascending thin limb of Henle's loop. Peer-reviewed

Fujiwara I, Kondo Y, Igarashi Y, Inoue C N, Takahashi N, Tada K, Abe K

Am J Physiol　268　(3 Pt 2)　F410-5　1995/03
CHARACTERIZATION OF NA+ TRANSPORT ACROSS THE CELL-MEMBRANES OF THE ASCENDING THIN LIMB OF HENLES LOOP Peer-reviewed

N TAKAHASHI, Y KONDO, FUJIWARA, I, O ITO, Y IGARASHI, K ABE

KIDNEY INTERNATIONAL　47　(3)　789-794　1995/03

ISSN： 0085-2538
Fujiwara I, Kondo Y, Igarashi Y, Inoue CN, Takahashi N, Tada K, Abe K. Peer-reviewed

268　(3Pt2)　F410-F415　1995/03
FUNCTIONAL DIFFERENCE BETWEEN 2 ISOFORMS OF RAT-KIDNEY PROSTAGLANDIN RECEPTOR-EP(3) SUBTYPE Peer-reviewed

K TAKEUCHI, N TAKAHASHI, T ABE, O ITO, E TSUTSUMI, Y TANIYAMA, K ABE

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS　203　(3)　1897-1903　1994/09

ISSN： 0006-291X
INSULIN STIMULATES NACL TRANSPORT IN ISOLATED-PERFUSED MTAL OF HENLES LOOP OF RABBIT KIDNEY Peer-reviewed

O ITO, Y KONDO, N TAKAHASHI, K KUDO, Y IGARASHI, K OMATA, Y IMAI, K ABE

AMERICAN JOURNAL OF PHYSIOLOGY　267　(2)　F265-F270　1994/08

ISSN： 0002-9513
DIFFERENT CELLULAR MECHANISMS OF VASOPRESSIN RECEPTOR V1 AND V2 SUBTYPE IN VASOPRESSION-INDUCED ADENOSINE-3',5'-MONOPHOSPHATE FORMATION IN AN IMMORTALIZED RENAL TUBULE CELL-LINE, TKC2 Peer-reviewed

K TAKEUCHI, N YANAI, N TAKAHASHI, T ABE, E TSUTSUMI, M OBINATA, K ABE

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS　202　(2)　680-687　1994/07

ISSN： 0006-291X
2 ISOFORMS OF THE RAT-KIDNEY EP3 RECEPTOR DERIVED BY ALTERNATIVE RNA SPLICING - INTRARENAL EXPRESSION COLOCALIZATION Peer-reviewed

K TAKEUCHI, N TAKAHASHI, T ABE, K ABE

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS　199　(2)　834-840　1994/03

ISSN： 0006-291X
ELECTROPHYSIOLOGICAL ANALYSIS OF EFFECT OF PROPRANOLOL IN RABBIT S2-PROXIMAL STRAIGHT TUBULE Peer-reviewed

Y KONDO, Y IGARASHI, K KUDO, N TAKAHASHI, O ITO, CN INOUE, FUJIWARA, I, K ABE

TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE　172　(1)　29-38　1994/01

ISSN： 0040-8727

eISSN： 1349-3329
MOLECULAR-CLONING AND INTRARENAL LOCALIZATION OF RAT PROSTAGLANDIN-E2 RECEPTOR EP3 SUBTYPE Peer-reviewed

K TAKEUCHI, T ABE, N TAKAHASHI, K ABE

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS　194　(2)　885-891　1993/07

ISSN： 0006-291X
Takeuchi K, Abe T, Takahashi N, Abe K. Peer-reviewed

Molecular cloning, intrarenal localization of, ra, rostaglandin, receptor EP, subtype

Biochem Biophys Res Commun.　194　(2)　885-891　1993/07
LACK OF DIRECT ACTION OF ATRIOPEPTIDASE INHIBITOR ON CELLULAR PH REGULATION IN RABBIT S2 PROXIMAL STRAIGHT TUBULES Peer-reviewed

N TAKAHASHI, Y KONDO, K KUDO, Y IGARASHI, O ITO, K ABE

TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE　169　(4)　261-270　1993/04

ISSN： 0040-8727

eISSN： 1349-3329
Insulin stimulates luminal Na/H antiport in rabbit proximal S2 straight tubules. Peer-reviewed

Takahashi N, Kondo Y, Ito O, Igarashi Y, Abe K

Nutr. Metab. Cardiovasc. Dis.　3　73-77　1993

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Misc. 92

アドリアマイシン誘発性腎症へのニコチンアミドの効果の検討

大金美月, 高橋慧, 山越聖子, 高橋信行, 佐藤恵美子

日本腎臓学会誌(Web)　67　(4)　2025

ISSN： 1884-0728
モデルマウスを用いた慢性腎臓病合併サルコペニアの病態解明

原秋夕希, 三枝大輔, 山越聖子, 高橋信行, 佐藤恵美子

日本腎臓学会誌(Web)　67　(4)　2025

ISSN： 1884-0728
慢性腎臓病における凝固・補体経路の役割とnicotinamideの治療効果

金沙織, 大江佑治, 小原拓, 佐藤恵美子, 高橋信行, 田中哲洋

日本腎臓学会誌(Web)　67　(4)　2025

ISSN： 1884-0728
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
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
低出生体重が及ぼす将来の妊娠への影響モデルマウスを用いた胎仔および胎盤の評価

山本真莉, 堰本晃代, 大川雅敬, 高橋信行, 佐藤恵美子

DOHad研究(Web)　10　(2)　2022

ISSN： 2187-2597
低出生体重が及ぼす将来の妊娠への影響モデルマウスを用いた母体の評価

大川雅敬, 堰本晃代, 山本真莉, 高橋信行, 佐藤恵美子

DOHad研究(Web)　10　(2)　2022

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Tadalafil投与が子宮灌流圧低下マウスの仔の出生体重と腎発達不全に与える影響

猿山春花, 堰本晃代, 高相陽子, 高橋信行, 佐藤恵美子

DOHad研究(Web)　10　(2)　2022

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ラクトフェリン投与による慢性腎臓病およびその合併症の進行抑制効果

岩本千奈, 堰本晃代, 高橋信行, 佐藤恵美子

日本腎臓学会誌(Web)　64　(3)　2022

ISSN： 1884-0728
Evaluation of intracellular metabolic alteration in uremic toxin exposure neurons and renal failure mouse brain

佐藤恵美子, 佐藤恵美子, 渡辺真由, 熊倉慧, 高橋信行, 高橋信行

JSBMS Letters　46　(Supplement)　2021

ISSN： 1881-5464
Evaluation of the effect of Methylglyoxal on metabolic alternation in myoblast cells

細田祐衣, 渡辺真由, 堰本晃代, 高橋信行, 佐藤恵美子

JSBMS Letters　46　(Supplement)　2021

ISSN： 1881-5464
ウレミックトキシンが凝固線溶系因子発現に及ぼす影響

大江佑治, 佐藤恵美子, 佐藤博, 宮崎真理子, 伊藤貞嘉, 高橋信行

日本腎臓学会誌(Web)　63　(4)　2021

ISSN： 1884-0728
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 　

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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.
ニコチンアミドは炎症の抑制によりアデニン腎症発生を予防する.

熊倉慧, 佐藤恵美子, 堰本晃代, 大江佑治, 宮崎真理子, 高橋信行

日本腎臓学会誌(Web)　62　(4)　2020

ISSN： 1884-0728
単球・マクロファージ由来組織因子の慢性腎臓病における役割

山陰周, 大江佑治, 佐藤恵美子, 堰本晃代, 岡本好司, 宮崎真理子, 佐藤博, 伊藤貞嘉, 高橋信行

日本腎臓学会誌(Web)　62　(4)　2020

ISSN： 1884-0728
内皮型NO合成酵素欠損はCKD関連異所性石灰化を誘導する

大江佑治, 佐藤恵美子, 宮崎真理子, 岡本好司, 佐藤博, 伊藤貞嘉, 高橋信行

日本腎臓学会誌(Web)　62　(4)　2020

ISSN： 1884-0728
カルボニルストレス誘導筋細胞内代謝変化のGC-MSによる評価

佐藤恵美子, 佐藤恵美子, 等々力崇太, 山本多恵, 宮崎真理子, 森建文, 伊藤貞嘉, 佐藤博, 佐藤博, 高橋信行, 高橋信行

JSBMS Letters　44　(Supplement)　2019

ISSN： 1881-5464
肥満に対するアルドステロンの影響-小腸におけるグルコース吸収の役割-

白井英和, 内田多恵子, 橋爪大和, 大屋咲子, 堰本晃代, 大江佑治, 佐藤恵美子, 佐藤恵美子, 佐藤博, 佐藤博, 伊藤貞嘉, 高橋信行, 高橋信行

日本高血圧学会総会プログラム・抄録集(CD-ROM)　42nd　2019
腎不全マウスの腸内細菌叢と腸内腐敗物の変化とAST-120による影響

佐藤恵美子, 細見晃司, 三枝大輔, 堰本晃代, 國澤純, 丹羽利充, 佐藤博, 高橋信行

JSBMS Letters　43　(Suppl.)　98-98　2018/08
Publisher: (一社)日本医用マススペクトル学会
ISSN： 1881-5464
Protease‐Activated receptor(PAR2)のCKDにおける役割

佐藤恵美子, 高橋信行

宮城県腎臓協会会報　(29)　83　2018/07/31

ISSN： 2432-3101
sFlt-1過剰発現妊娠高血圧腎症モデルマウスでアシルカルニチンが上昇する機序

佐藤恵美子, 金子茉那美, 津國由佳子, 伏間智史, 三枝大輔, 堰本晃代, 伊藤貞嘉, 佐藤博, 高橋信行

日本腎臓学会誌　60　(3)　334-334　2018/04
Publisher: (一社)日本腎臓学会
ISSN： 0385-2385
血液凝固系に関連した糖尿病性腎症早期診断・薬効マーカー

佐藤恵美子, 大江佑治, 佐藤博, 伊藤貞嘉, 高橋信行

日本腎臓学会誌　60　(3)　402-402　2018/04
Publisher: (一社)日本腎臓学会
ISSN： 0385-2385
新規全身性エリテマトーデス合併妊娠高血圧腎症モデルマウスの開発

伊丸岡健太, 大江佑治, 伏間智史, 佐藤恵美子, 佐藤恵美子, 佐藤博, 佐藤博, 菅原準一, 伊藤貞嘉, 高橋信行, 高橋信行

日本高血圧学会総会プログラム・抄録集　40th　362-362　2017/10/20
Publisher: (NPO)日本高血圧学会
Reduced Uterine Perfusion Pressure(RUPP)preeclampsia(PE)モデルにおけるマウス系統および術式の検討

堰本晃代, 堰本晃代, 伏間智史, 大江佑治, 佐藤恵美子, 佐藤恵美子, 伊藤貞嘉, 佐藤博, 佐藤博, 高橋信行, 高橋信行

日本高血圧学会総会プログラム・抄録集　40th　362　2017/10/20
sFlt‐1過剰発現eNOS欠損マウスは重症肝障害と血小板減少症を発症する

大江佑治, 伏間智史, 佐藤恵美子, 佐藤恵美子, 佐藤博, 佐藤博, 菅原準一, 伊藤貞嘉, 高橋信行, 高橋信行

日本高血圧学会総会プログラム・抄録集　40th　362-362　2017/10/20
Publisher: (NPO)日本高血圧学会
新規全身性エリテマトーデス合併妊娠高血圧腎症モデルマウスの開発

大江佑治, 大江佑治, 伊丸岡健太, 伏間智史, 佐藤恵美子, 佐藤恵美子, 佐藤博, 佐藤博, 菅原準一, 伊藤貞嘉, 高橋信行, 高橋信行

日本妊娠高血圧学会雑誌　24　74-74　2017/09
Publisher: (一社)日本妊娠高血圧学会
ISSN： 1880-3172
sFlt‐1過剰発現eNOS欠損マウスは重症肝障害と血小板減少症を発症する

大江佑治, 大江佑治, 伏間智史, 佐藤恵美子, 佐藤恵美子, 佐藤博, 佐藤博, 菅原準一, 伊藤貞嘉, 高橋信行, 高橋信行

日本妊娠高血圧学会雑誌　24　60-60　2017/09
Publisher: (一社)日本妊娠高血圧学会
ISSN： 1880-3172
RUPP PEモデルにおけるマウス系統および術式の検討

堰本晃代, 堰本晃代, 伏間智史, 大江佑治, 佐藤恵美子, 佐藤恵美子, 伊藤貞嘉, 佐藤博, 佐藤博, 高橋信行, 高橋信行

日本妊娠高血圧学会雑誌　24　73　2017/09

ISSN： 1880-3172
新規Reduced Uterine Perfusion Pressure(RUPP)PEモデルの開発におけるマウス系統の重要性

堰本晃代, 伏間智史, 大江佑治, 佐藤恵美子, 伊藤貞嘉, 佐藤博, 高橋信行

日本腎臓学会誌　59　(3)　304　2017/04/25

ISSN： 0385-2385
ニコチンアミドによる妊娠高血圧腎症治療におけるCD38の役割

高橋信行, 石田晃規, 伏間智史, 増島直弥, 堰本晃代, 佐藤恵美子, 佐藤博, 伊藤貞嘉

日本腎臓学会誌　59　(3)　233　2017/04/25

ISSN： 0385-2385
アデニン腎症におけるプロテアーゼ活性化受容体2の役割

林咲貴子, 大江佑治, 伏間智史, 佐藤恵美子, 佐藤博, 伊藤貞嘉, 高橋信行

日本腎臓学会誌　59　(3)　290　2017/04/25

ISSN： 0385-2385
新規全身性エリテマトーデス合併妊娠高血圧腎症モデルマウスの作製

伊丸岡健太, 大江佑治, 伏間智史, 佐藤恵美子, 佐藤博, 菅原準一, 伊藤貞嘉, 高橋信行

日本腎臓学会誌　59　(3)　360-360　2017/04/25
Publisher: (一社)日本腎臓学会
ISSN： 0385-2385

eISSN： 1884-0728
妊娠高血圧腎症モデルマウスにおけるプロテアーゼ活性化受容体2の役割

小畑裕史, 江美恵子, 大江佑治, 伏間智史, 佐藤恵美子, 佐藤博, 伊藤貞嘉, 高橋信行

日本腎臓学会誌　59　(3)　305　2017/04/25

ISSN： 0385-2385
上皮‐内皮クロストーク機構の破綻と肝腎障害の新規メカニズム

大江佑治, 伏間智史, 佐藤恵美子, 佐藤博, 菅原準一, 伊藤貞嘉, 高橋信行

日本腎臓学会誌　59　(3)　230-230　2017/04/25
Publisher: (一社)日本腎臓学会
ISSN： 0385-2385

eISSN： 1884-0728
ニコチンアミドによるIgA腎症合併妊娠への治療効果

伏間智史, 堰本晃代, 大江佑治, 佐藤恵美子, 鈴木祐介, 佐藤博, 伊藤貞嘉, 高橋信行

日本腎臓学会誌　59　(3)　305　2017/04/25

ISSN： 0385-2385
メタボロミクスによるsFlt‐1過剰発現妊娠高血圧腎症モデルマウスの病態解析

金子茉那美, 佐藤恵美子, 津國由佳子, 伏間智史, 三枝大輔, 堰本晃代, 伊藤貞嘉, 佐藤博, 高橋信行

日本腎臓学会誌　59　(3)　230-230　2017/04/25
Publisher: (一社)日本腎臓学会
ISSN： 0385-2385

eISSN： 1884-0728
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
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
メタボロミクスによるsFlt-1過剰発現妊娠高血圧腎症モデルマウスの病態解析

金子茉那美, 佐藤恵美子, 津國由佳子, 伏間智史, 三枝大輔, 堰本晃代, 伊藤貞嘉, 佐藤博, 高橋信行

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
慢性腎臓病におけるプロテアーゼ活性化受容体2の役割

林咲貴子, 大江佑治, 伏間智史, 佐藤恵美子, 佐藤恵美子, 佐藤博, 佐藤博, 伊藤貞嘉, 高橋信行, 高橋信行

日本薬学会年会要旨集(CD-ROM)　137th　ROMBUNNO.27I‐am13S　2017
妊娠高血圧腎症の新規薬物治療

高橋信行, 高橋信行, 伏間智史, 大柳元, 佐藤恵美子, 佐藤恵美子, 中田宏伸, 大江佑治, 堰本晃代, 堰本晃代, 三枝大輔, 佐藤博, 佐藤博, 伊藤貞嘉, LI Feng, JENNETTE JC, 前田信代, KARUMANCHI Ananth, SMITHIES Oliver

日本薬学会年会要旨集(CD-ROM)　137th　(4)　ROMBUNNO.25F‐pm16-57　2017
Publisher: (公社)日本薬学会
ISSN： 0918-9823
LPS投与妊娠高血圧腎症モデルマウスにおけるプロテアーゼ活性化受容体2の役割

江美恵子, 小畑裕史, 大江佑治, 大江佑治, 伏間智史, 佐藤恵美子, 佐藤恵美子, 佐藤博, 佐藤博, 伊藤貞嘉, 高橋信行, 高橋信行

日本高血圧学会総会プログラム・抄録集　39th　325　2016/09/30
C57BL/6Jマウスでの新規Reduced Uterine Perfusion Pressure(RUPP)モデルの開発

堰本晃代, 堰本晃代, 伏間智史, 大江佑治, 大江佑治, 佐藤恵美子, 佐藤恵美子, 伊藤貞嘉, 佐藤博, 佐藤博, 高橋信行, 高橋信行

日本高血圧学会総会プログラム・抄録集　39th　342　2016/09/30
eNOS欠損糖尿病性腎症モデルマウスにおける血液凝固第Xa因子‐プロテアーゼ活性化受容体2の役割

大江佑治, 林咲貴子, 伏間智史, 佐藤恵美子, 佐藤恵美子, 金須清美, 佐藤博, 佐藤博, 伊藤貞嘉, 高橋信行, 高橋信行

日本高血圧学会総会プログラム・抄録集　39th　325　2016/09/30
IgA腎症は妊娠により増悪し,妊娠高血圧腎症の危険因子となる

伏間智史, 大江佑治, 佐藤恵美子, 佐藤恵美子, 鈴木祐介, 富野康日己, 伊藤貞嘉, 佐藤博, 佐藤博, 高橋信行, 高橋信行

日本高血圧学会総会プログラム・抄録集　39th　342　2016/09/30
ニコチンアミドの妊娠高血圧腎症治療効果におけるヘムオキシゲナーゼの役割

高橋信行, 高橋信行, 中田宏伸, 伏間智史, 堰本晃代, 堰本晃代, 大江佑治, 佐藤恵美子, 佐藤恵美子, 佐藤博, 佐藤博, 伊藤貞嘉

日本妊娠高血圧学会雑誌　23　67　2016/09

ISSN： 1880-3172
C57BL/6Jマウスでの新規Reduced Uterine Perfusion Pressure(RUPP)モデルの開発

伏間智史, 堰本晃代, 大江佑治, 佐藤恵美子, 佐藤恵美子, 伊藤貞嘉, 佐藤博, 佐藤博, 高橋信行, 高橋信行

日本妊娠高血圧学会雑誌　23　68　2016/09

ISSN： 1880-3172
メタボロミクスによるsFlt-1過剰発現妊娠高血圧腎症モデルマウスの病態解析

佐藤恵美子, 津國由佳子, 伏間智史, 金子茉那美, 三枝大輔, 堰本晃代, 伊藤貞嘉, 佐藤博, 高橋信行

日本高血圧学会総会プログラム・抄録集　39回　324-324　2016/09
Publisher: (NPO)日本高血圧学会
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
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
新規Reduced Uterine Perfusion Pressure(RUPP)マウスモデルの開発

伏間智史, 堰本晃代, 大江佑治, 佐藤恵美子, 伊藤貞嘉, 佐藤博, 高橋信行

日本腎臓学会誌　58　(3)　303　2016/05/10

ISSN： 0385-2385
ニコチンアミドがPEに伴うFGRを改善する機序

高橋信行, 高橋信行, 伏間智史, 佐藤恵美子, 佐藤恵美子, 佐藤博, 佐藤博, 伊藤貞嘉

日本妊娠高血圧学会雑誌　23　2016

ISSN： 1880-3172
ニコチンアミドはAsb4欠損マウスの妊娠高血圧腎症,妊娠の維持,およびに胎児生存率を改善する

高橋信行, 高橋信行, 高橋信行, 伏間智史, LI Feng, 大江佑治, 佐藤恵美子, 佐藤恵美子, 佐藤博, 佐藤博, 伊藤貞嘉

日本高血圧学会総会プログラム・抄録集　38th　405　2015/10/09
ニコチンアミドはAsb4欠損マウスのPE,妊娠の維持,およびに胎児生存率を改善する

高橋信行, 伏間智史, LI Feng, 大江佑治, 佐藤恵美子, 佐藤博, 伊藤貞嘉

日本妊娠高血圧学会雑誌　22　72　2015/08

ISSN： 1880-3172
妊娠高血圧腎症におけるカルニチン代謝の変化

津國由佳子, 佐藤恵美子, 内田多恵子, 伏間智史, 三枝大輔, 佐藤博, 高橋信行

日本妊娠高血圧学会雑誌　22　72-72　2015/08
Publisher: (一社)日本妊娠高血圧学会
ISSN： 1880-3172
新規Reduced Uterine Perfusion Pressure(RUPP)マウスモデルの開発

伏間智史, 堰本晃代, 大江祐治, 金子茉那美, 佐藤恵美子, 伊藤貞嘉, 佐藤博, 高橋信行

日本妊娠高血圧学会雑誌　22　73　2015/08

ISSN： 1880-3172
IgA腎症は妊娠予後を悪化させ,妊娠はIgA腎症を悪化させる(マウスモデルでの検討)

伏間智史, 大江佑治, 佐藤恵美子, 鈴木祐介, 富野康日己, 伊藤貞嘉, 佐藤博, 高橋信行

日本妊娠高血圧学会雑誌　22　73　2015/08

ISSN： 1880-3172
メタボローム解析による妊娠高血圧腎症治療標的分子の探索

津國由佳子, 佐藤恵美子, 伏間智史, 佐藤博, 高橋信行, 三枝大輔

JSBMS Letters　40　(Suppl.)　73-73　2015/08
Publisher: (一社)日本医用マススペクトル学会
ISSN： 1881-5464
IgA腎症は妊娠予後を悪化させ,妊娠はIgA腎症を悪化させる(マウスモデルにおける検討)

伏間智史, 大江佑治, 佐藤恵美子, 鈴木祐介, 富野康日己, 伊藤貞嘉, 佐藤博, 高橋信行

日本腎臓学会誌　57　(3)　503　2015/04/30

ISSN： 0385-2385
糖尿病性腎症におけるプロテアーゼ活性化受容体2(PAR2)の役割

大江佑治, 佐藤恵美子, 佐藤博, 伊藤貞嘉, 高橋信行

日本腎臓学会誌　57　(3)　502　2015/04/30

ISSN： 0385-2385
レセプトデータを用いた東北大学病院の本態性高血圧患者における降圧薬の処方動向調査

黒澤桂子, 佐藤倫広, 飯田優太郎, 小原拓, 松浦正樹, 井上隆輔, 高橋信行, 佐藤博, 村井ユリ子, 眞野成康

日本薬学会年会要旨集　135年会　(4)　134-134　2015/03
Publisher: (公社)日本薬学会
ISSN： 0918-9823
一般地域住民におけるセルフメディケーションの実態とその要因に関する調査大迫研究

佐藤倫広, 松本章裕, 原梓, 岩森紗希, 小原拓, 菊谷昌浩, 目時弘仁, 保坂実樹, 淺山敬, 高橋信行, 佐藤博, 眞野成康, 今井潤, 大久保孝義

薬学雑誌　134　(12)　1347-1355　2014/12
Publisher: (公社)日本薬学会
ISSN： 0031-6903

eISSN： 1347-5231

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一般地域住民におけるセルフメディケーションの実態とその要因について検討した。大迫町の一般地域住民1008例を対象とした。OTC・サプリメントの使用経験があったものは519例(51.5%)であった。使用したことのあるOTCとして、風邪薬、目薬、湿布が、サプリメントの健康食品や栄養ドリンクが高率に挙げられた。OTC・サプリメント使用経験がある者で、女性及び脂質異常症既往者が高率で、現在喫煙者が低率であった。家庭血圧は、OTC・サプリメント使用経験がある者で低値であった。OTC・サプリメント使用経験の規定因子として、女性、配置販売業者の訪問回数(年に2〜3回以上)、脂質異常症あり.及び家庭収縮期血圧低値が選択された。降圧薬服用量において、家庭血圧とOTC・サプリメント使用経験との間に負の関連を認めた。
新規高感度ヘムオキシゲナーゼ活性測定法の開発

岩森紗希, 佐藤恵美子, 吉成浩一, 島田美樹, 眞野成康, 伊藤貞嘉, 佐藤博, 高橋信行

日本高血圧学会総会プログラム・抄録集　37回　332-332　2014/10
Publisher: (NPO)日本高血圧学会
新規高感度ヘムオキシゲナーゼ活性測定法の開発

岩森紗希, 佐藤恵美子, 吉成浩一, 島田美樹, 眞野成康, 伊藤貞嘉, 佐藤博, 高橋信行

JSBMS Lett　39　(Supplement)　98-98　2014/09/01
Publisher: (一社)日本医用マススペクトル学会
ISSN： 1881-5464
新規高感度ヘムオキシゲナーゼ活性測定法の開発

岩森紗希, 佐藤恵美子, 吉成浩一, 島田美樹, 眞野成康, 伊藤貞嘉, 佐藤博, 高橋信行

日本腎臓学会誌　56　(3)　283-283　2014/05/25
Publisher: (一社)日本腎臓学会
ISSN： 0385-2385

eISSN： 1884-0728
ニコチン酸アミドのIgA腎症に対する治療効果

伏間智史, 大江佑治, 岩森紗希, 佐藤恵美子, 鈴木裕介, 富野康日己, 伊藤貞嘉, 佐藤博, 高橋信行

日本腎臓学会誌　56　(3)　388　2014/05/25

ISSN： 0385-2385
日本の一般地域住民におけるセルフメディケーションに関する実態調査

佐藤倫広, 松本章裕, 原梓, 岩森紗希, 菊谷昌浩, 小原拓, 目時弘仁, 小野木弘志, 高橋信行, 佐藤博, 眞野成康, 今井潤, 大久保孝義

日本補完代替医療学会学術集会プログラム・抄録集　16th　58-58　2013/11
Publisher: 日本補完代替医療学会
土-P2-191 レニン・アンジオテンシン系阻害薬による貧血における甲状腺機能低下の関与(有害事象・副作用,一般演題ポスター発表,再興、再考、創ろう最高の医療の未来)

佐藤和幸, 佐藤博, 高橋信行, 佐藤倫広, Heak Aing

日本医療薬学会年会講演要旨集　23　283-283　2013/08/28
Publisher: 日本医療薬学会
一般地域住民におけるセルフメディケーションに関する実態調査

岩森紗希, 松本章裕, 佐藤倫広, 原梓, 菊谷昌浩, 小原拓, 目時弘仁, 廣瀬卓男, 井上隆輔, 浅山敬, 高橋信行, 眞野成康, 佐藤博, 今井潤, 大久保孝義

日本医療薬学会年会講演要旨集　23rd　354-354　2013/08/28
Publisher: 日本医療薬学会
バイタルサイン実習:高機能患者シミュレータを用いた疾患模擬処置を「見学型」から「実践型」に切り替えたことによる学生の学習意欲調査

橋本貴尚, 高橋信行, 佐藤恵美子, 村井ユリ子, 平澤典保, 富岡佳久, 栃窪克行, 佐藤博

日本医療薬学会年会講演要旨集　22nd　484-484　2012/10/10
Publisher: 日本医療薬学会
薬学生の臨床思考を醸成し実務実習へとつなげる事前学習の成果と今後の課題

橋本貴尚, 大久保孝義, 高橋信行, 村井ユリ子, 佐藤慶子, 寺田志保, 目時弘仁, 菊谷昌浩, 平澤典保, 富岡佳久, 大庭正敏, 今井潤, 佐藤博

医療薬学　38　(5)　322-331　2012

DOI： 10.5649/jjphcs.38.322 　
Changes in serum cholesterol, blood glucose, and blood pressure after administration of simvastatin:

Obara T, Igari Y, Kobayashi H, Takahashi T, Takahashi N, Kishikawa Y, Murai Y, Mano N, Takahashi M

J. Drug Interaction Res.　36　(2)　15-20　2012
薬学生の臨床思考を醸成し実務実習へとつなげる事前実習の成果と課題 : バイタル・心肺蘇生・副作用管理(一般演題(口頭)27,薬学教育(実務実習)(1),Enjoy Pharmacists' Lifestyles)

寺田志保, 橋本貴尚, 大久保孝義, 高橋信行, 村井ユリ子, 佐藤慶子, 目時弘仁, 菊谷昌浩, 平澤典保, 富岡佳久, 大庭正敏, 今井潤, 佐藤博

日本医療薬学会年会講演要旨集　21　162-162　2011/09/09
Publisher: 日本医療薬学会
A modest decrease in endothelial NOS in mice comparable to that associated with human NOS3 variants exacerbates diabetic nephropathy (vol 108, pg 2070, 2011)

Chih-Hong Wang, Feng Li, Sylvia Hiller, Hyung-Suk Kim, Nobuyo Maeda, Oliver Smithies, Nobuyuki Takahashi

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA　108　(5)　2011/02

DOI： 10.1073/pnas.1101346108 　

ISSN： 0027-8424
Increased susceptibility to heart failure in mice lacking natriuretic peptide receptor-A gene

T Nishikimi, Hagaman, JR, N Takahashi, HS Kim, H Matsuoka, O Smithies, N Maeda

CIRCULATION　110　(17)　21-21　2004/10

ISSN： 0009-7322
Mice lacking renin are hypotensive, excrete dilute urine, and are unresponsive to DDAVP.

N Takahashi, G Lee, RA Gomez, HS Kim, O Smithies

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY　14　29A-29A　2003/11

ISSN： 1046-6673
A computer simulation of the NKCC2+/- phenotype

N Takahashi, O Smithies

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY　14　777A-777A　2003/11

ISSN： 1046-6673
【分子高血圧最新の進歩】15-deoxy-Δ12,14-プロスタグランジンJ2及びトログリタゾンによるトロンボキサン受容体遺伝子の負の転写調節

菅原明, 竹内和久, 宇留野晃, 池田勧夫, 工藤正孝, 谷山佳弘, 高橋信行, 阿部倫明, 伊藤貞嘉

血圧　6　(3)　213-215　1999/03
Publisher: (株)先端医学社
ISSN： 1340-4598

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15-deoxy-Δ12,14-PGJ2はTXR mRNAの発現を抑制し,トログリタゾンと同様TXR遺伝子プロモーター活性を低下させたことから,これらがTXR遺伝子を転写レベルで抑制しているものと考えられた.TXRの発現抑制は,高血圧や動脈硬化の進展抑制に関与している可能性が推定された
Mutation analysis or human thiazide-sensitive Na-Cl cotransporter

Y Taniyama, K Takeuchi, A Sugawara, N Takahashi, T Kato, Y Ikeda, K Abe, S Ito

JOURNAL OF HYPERTENSION　16　S38-S38　1998/06

ISSN： 0263-6352
A mutation in thiazide-sensitive Na-Cl cotransporter is associated with familial Gitelman's syndrome.

K Takeuchi, T Kato, N Takahashi, Y Taniyama, K Abe

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY　7　(9)　A0542-A0542　1996/09

ISSN： 1046-6673
Structure and transcriptional function of the 5'-flanking region of rat thromboxane receptor gene.

N Takahashi, K Takeuchi, T Kato, Y Taniyama, T Abe, K Abe

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY　7　(9)　A2012-A2012　1996/09

ISSN： 1046-6673

eISSN： 1533-3450
IMMUNOHISTOCHEMICAL LOCALIZATION OF THROMBOXANE RECEPTOR AND THROMBOXANE SYNTHASE IN RAT-KIDNEY

N TAKAHASHI, K TAKEUCHI, T ABE, E TSUTSUMI, K ABE

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY　6　(3)　762-762　1995/09

ISSN： 1046-6673
EFFECTS OF INTRACELLULAR PH AND CA2+ ON CL- TRANSPORT IN THE ASCENDING THIN LIMB (ATL)

M OBA, Y IGARASHI, N TAKAHASHI, T KONDO, K ABE

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY　6　(3)　348-348　1995/09

ISSN： 1046-6673
Role of calcium in insulin-stimulated NaC1 transport in medullary thick ascending limb. International-journal

O Ito, Y Kondo, N Takahashi, K Omata, K Abe

The American journal of physiology　269　(2 Pt 2)　F236-41　1995/08

ISSN： 0002-9513

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It has been reported that insulin stimulates directly NaCl transport in the rabbit medullary thick ascending limb (MTAL) [O. Ito, Y. Kondo, N. Takahashi, K. Kudo, Y. Imai, K. Omata, and K. Abe. Am. J. Physiol. 267 (Renal Fluid Electrolyte Physiol. 36): F265-F270, 1994]. In the present investigation, we evaluated the role of Ca2+ in insulin-stimulated NaCl transport in rabbit MTAL by in vitro microperfusion methods. In control experiments, insulin increases transepithelial voltage (Vte) and net lumen-to-bath Cl-flux (JCl). The effects of insulin on Vte and JCl in a Ca2+ -free solution containing ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N' -tetraacetic acid did not differ from those in a Ca2+ -containing control solution. Direct measurements of cytosolic free Ca2+ ([Ca2+]i) with fura 2 fluorescence showed that insulin caused no detectable change in [Ca2+]i in MTAL cells. Chelation of intracellular Ca2+ with the acetoxymethyl ester of 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid inhibited the actions of insulin in Vte and JCl without affecting basal values. We examined further whether calmodulin is also involved in insulin-stimulated NaCl transport in MTAL using two dissimilar inhibitors of calmodulin, trifluoperazine (TFP) and N-(6-aminohexyl)-5-chloro-1-naphthalene-sulfonamide (W-7). TFP and W-7 inhibited the action of insulin in a dose-dependent manner, with maximal inhibition of both agents of > 90%. The half-maximal inhibition by TFP and W-7 was approximately 50 and 100 microM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Electrolyte metabolism in renal tubules

N. Takahashi, O. Ito, Y. Kondo, K. Abe

Nippon rinsho. Japanese journal of clinical medicine　53　1868-1872　1995/08/01

ISSN： 0047-1852
Cytosolic Ca2+ dynamics in hamster ascending thin limb of Henle's loop. International-journal

N Takahashi, Y Kondo, O Ito, Y Igarashi, K Omata, K Abe

The American journal of physiology　268　(6 Pt 2)　F1148-53　1995/06

ISSN： 0002-9513

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Intracellular calcium plays an important role in the regulation of Cl- reabsorption in the ascending thin limb of Henle's loop (ATL). To elucidate the cytosolic Ca2+ dynamics in the ATL, intracellular Ca2+ concentration activity ([Ca2+]i) was measured in the in vitro microperfused hamster ATL using fura 2. Basal [Ca2+]i was 89.1 +/- 7.3 nM (n = 9 tubules). Removal of Ca2+ from the peritubular solution decreased [Ca2+]i from 89.1 +/- 7.3 to 64.1 +/- 7.1 nM in 2 min (n = 9, P < 0.05), whereas [Ca2+]i did not change after removal of Ca2+ from the luminal solution. Addition of 1 mM NaCN to the bath increased [Ca2+]i. This effect was completely abolished by the elimination of ambient Ca2+. Trifluoperazine and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) in the bath reversibly increased [Ca2+]i, whereas addition of 1 mM ouabain to the bath decreased [Ca2+]i. Rates of changes in [Ca2+]i after removal and replacement of basolateral Ca2+ were not affected by removal of Na+, K+, or Cl- from the bath, whereas nicardipine decreased these parameters. Increasing bath K+ from 5 to 100 mM decreased [Ca2+]i from 69.3 +/- 5.8 to 50.8 +/- 5.0 nM in 1 min (n = 6, P < 0.05). Subsequent reduction of K+ from 100 to 5 mM increased [Ca2+]i to 174.0 +/- 30.8 nM in 1 min, followed by a gradual decrease in [Ca2+]i to a steady-state level of 74.2 +/- 8.0 nM in 2 min. Changes in basolateral K+ concentration did not affect [Ca2+]i in the absence of ambient Ca2+.(ABSTRACT TRUNCATED AT 250 WORDS)
尿細管間質性腎症基礎研究の進歩尿細管間質細胞における代謝様式 (日本臨床)

高橋信行, 伊藤修, 根東義明, 他

日本臨床　53　(8)　1868-1872　1995
CHARACTERIZATION OF NA+ TRANSPORT ACROSS THE LUMINAL MEMBRANE OF THE ASCENDING THIN LIMB OF HENLES LOOP

N TAKAHASHI, Y KONDO, O ITO, Y IGARASHI, K OMATA, K ABE

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY　5　(3)　301-301　1994/09

ISSN： 1046-6673
VASOPRESSIN STIMULATES CL TRANSPORT IN THE ASCENDING THIN LIMB OF HENLES LOOP

N TAKAHASHI, Y KONDO, O ITO, Y IGARASHI, K OMATA, K ABE

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY　5　(3)　279-279　1994/09

ISSN： 1046-6673
AUTOCRINE THROMBOXANE SYSTEM IN THE RENAL GLOMERULUS

K TAKEUCHI, T ABE, E TSUTSUMI, K OMATA, N TAKAHASHI, K ABE

HYPERTENSION　24　(3)　409-409　1994/09

ISSN： 0194-911X
Insulin stimulates NaCl transport in isolated perfused MTAL of Henle's loop of rabbit kidney

Osamu Ito, Yoshiaki Kondo, Nobuyuki Takahashi, Kei Kudo, Yutaka Igarashi, Ken Omata, Yutaka Imai, Keishi Abe

American Journal of Physiology - Renal Fluid and Electrolyte Physiology　267　1994/08/30

ISSN： 0363-6127
RAT-KIDNEY PROSTAGLANDIN-E2 RECEPTOR-EP3 SUBTYPE - MOLECULAR-CLONING AND INTRARENAL LOCALIZATION

K TAKEUCHI, T ABE, N TAKAHASHI, K ABE

HYPERTENSION　22　(3)　409-409　1993/09

ISSN： 0194-911X

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Industrial Property Rights 2

妊娠高血圧症モデル動物

髙橋信行

Property Type: Patent
ニコチンアミドによる妊娠高血圧症候群、流産・早産、及び胎児発育不全の改善

髙橋信行

Property Type: Patent

Research Projects 12

ヒストン脱メチル化酵素欠損と胎生致死および新規妊娠高血圧腎症モデルの開発

高橋信行, 佐藤恵美子, 山越聖子

Offer Organization: 日本学術振興会

System: 科学研究費助成事業

Category: 基盤研究(C)

Institution: 東北大学

2024/04/01 - 2029/03/31
ニコチンアミドによる慢性腎臓病の治療・予防と新規治療薬の開発

高橋信行, 佐藤恵美子, 堰本晃代

Offer Organization: 日本学術振興会

System: 科学研究費助成事業

Category: 基盤研究(C)

Institution: 東北大学

2021/04/01 - 2024/03/31

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腎臓で血液をろ過する糸球体の障害をきっかけとして、徐々に腎臓全体が障害されて腎不全になるタイプの慢性腎臓病は多い。しかし、その病態には不明な点が多く、治療法も確立していない。最近、研究代表者らは腎臓で体液の水分塩分などの量の調節を行う尿細管という部分の障害による慢性腎臓病をビタミンB3であるナイアシン（ニコチンアミド）がATP産生を増加することなどによって予防することを明らかにした。抗ガン剤のアドリアマイシンによっておこる動物モデルは糸球体障害による慢性腎臓病の研究によく用いられている。本研究ではアドリアマイシンによっておこる糸球体障害がニコチンアミドで予防や治療ができるか明らかにすることを目的とした。当該年度の研究において、マウスにアドリアマイシンを投与すると、ネフローゼ症候群に匹敵する大量の蛋白（アルブミン）の尿中への排泄が認められた。次に、糸球体障害による慢性腎臓病で患者数も多いIgA腎症に注目した。IgA腎症は腎不全へ進行し、透析などが必要になることが少なくない。さらに、IgA腎症は妊娠可能年齢の女性にも多い。本研究において、IgA腎症に対するニコチンアミドの効果を明らかにすることを目的として、IgA腎症のマウスモデルであるgddYマウスを用いた。gddYマウスのオスへのニコチンアミド投与は、腎機能、腎病理所見を改善しなかったが、生存率、炎症性サイトカインや線維化に関連する遺伝子の腎臓での発現を低下させた。また、メスgddYマウスの正常妊娠および妊娠高血圧症候群（妊娠中毒症）のモデルを作成した。ニコチンアミドは、妊娠高血圧症候群とIgA腎症の進行を抑制する傾向をもたらした。
Elucidating the pathogenic mechanism of CKD-associated cognitive dysfunction and muscle wasting as revealed by metabolic changes in organs

Sato Emiko

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

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

Institution: Tohoku University

2019/04/01 - 2022/03/31

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Chronic kidney disease (CKD)-associated cognitive dysfunction and muscle wasting are important problems with the aging of the patients with CKD. In this study, we elucidated the pathogenesis of CKD-associated cognitive dysfunction and muscle wasting using cell line and animal disease model. We first evaluated the effects of various uremic toxins on the mouse myoblast cell line C2C12 and the mouse hippocampal neuronal cell line HT-22. We found that indoxyl sulfate and indole negatively affected the hippocampal neuronal cell line, and that methylglyoxal induced intracellular metabolic changes and decreased ATP production in only myoblasts. Furthermore, we found that intracellular metabolic changes are also induced in the kidney in CKD model mouse, and that nicotinamide treatment protect the progression of the CKD dysfunction.
Development of a new model mouse for preeclampsia and establishment of placental / fetal blood vessel development evaluation method.

Sekimoto Akiyo

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

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

Institution: Tohoku University

2018/04/01 - 2021/03/31

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We improved the RUPP-PE modeling technique that we have succeeded in developing and combined it with transgenic mice to show a stable phenotype without using viruses, and it can be widely used for preeclampsia. We succeeded in developing a model of preeclampsia and creating a model of preeclampsia with different severity. Furthermore, in order to construct a method for evaluating the vascular development of stunted placenta, which is considered to be the cause of the onset of preeclampsia, we were able to establish a method for creating a placental vascular casting model.
Studies of therapeutic medicines for pregnancy complicated with renal disease

Sato Hiroshi

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

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

Institution: Tohoku University

2017/04/01 - 2020/03/31

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In this study, we focused on pregnancy with systemic lupus erythematosus (SLE) and IgA nephropathy as pregnancies with renal disease. These diseases are prevalent among women in their 20s and 40s who can be pregnant. In addition, pregnancy with these diseases is frequently associated with miscarriage/premature birth, fetal growth restriction, preeclampsia-like symptoms, etc., and pregnancy prognosis is poor. Therefore, it is an urgent need to develop new therapeutic medicines. We have already shown that nicotinamide, which is a vitamin B3, is a medicine that can be administrated to pregnant women and improves oxidative stress and endothelial dysfunction in preeclampsia model mice. In this study, we also found that nicotinamide showed therapeutic effects such as suppression of hypertension and improvement of fetal growth restriction in pregnancies with SLE or IgA.
Uremic sarcopenia induced by uremic toxins in chronic kidney disease

Sato Emiko

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

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

Institution: Tohoku University

2016/04/01 - 2019/03/31

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Sarcopenia is associated with increased morbidity and mortality in chronic kidney disease (CKD). Pathogenic mechanisms of skeletal muscle loss in CKD remains unclear. Renal dysfunction results in the accumulation of various uremic toxins in the circulation. The accumulation of uremic toxins has been proposed as a contributing factor for sarcopenia in CKD. In this study, we examined the association between uremic toxins and sarcopenia using myoblast cell line C2C12, adenine-induced renal failure model mouse, and CKD patients. From our results, it indicated that uremic toxin indoxyl sulfate is a pathogenic factor for sarcopenia in CKD. Futhermore, we revealed that causative pathological mechanism of uremic sarcopenia is metabolic alteration causes ATP shortage in muscle cells.
Search for novel physiological function of transcriptional factor Nrf2

Suzuki Takafumi, SEKI Shiori, HIRAMOTO Keiichiro, NAGANUMA Eriko, TAKAHASHI Nobuyuki, SATO Hiroshi, YAMAMOTO Masayuki

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

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

Institution: Tohoku University

2014/04/01 - 2017/03/31

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Nrf2 regulates the cellular response to oxidative/electrophilic stresses, and loss of Keap1 increases Nrf2 protein level. As Keap1-null mice die of esophageal hyperkeratosis, whole-body phenotypes of Nrf2 hyperactivation in adult animals remain to be delineated. To circumvent this problem, we deleted esophageal Nrf2 in Keap1-null mice. These mice survived until adulthood, but developed polyuria with low osmolality and bilateral hydronephrosis. This novel phenotype appears to be attributable to defects in water reabsorption caused by a reduction in the level of the AQP2 channel in the kidney. This phenotype was recapitulated by renal tubular deletion of Keap1, which generated symptoms of nephrogenic diabetes insipidus, demonstrating that Nrf2 activation in developing tubular cells causes a water reabsorption defect. Our approach to rescue mice from the lethal first hit of Keap1 ablation serves as a useful tool to study novel functions of Nrf2.
(Pro)renin receptor in renal and cardiovascular injuries.

TOTSUNE Kazuhito, TAKAHASI Kazuhiro, IMAI Yutaka, HIROSE Takuo, TAKAHASI Nobuyuki

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

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

Institution: Tohoku University

2013/04/01 - 2016/03/31

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Pathophysiological roles of (pro)renin receptor ((P)RR) were investigated in renal and cardiovascular injuries and cancers. This research project revealed that (1) soluble type (P)RR (sPRR) is present in human plasma and sPRR levels were elevated in patients with primary aldosteronism and Gittelman syndrome, (2) high sodium intake or dehydration induced (P)RR expression in rat kidneys, (3) (P)RR was associated with cancer proliferation, and (4) sPRR levels have an association with brain atrophy.
Role of ADP ribosyl cyclase in pathogenesis of preeclampsia

TAKAHASHI NOBUYUKI, SATO Hiroshi, SATO Emiko

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Challenging Exploratory Research

Institution: Tohoku University

2012/04/01 - 2014/03/31

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Pre-eclampsia (PE), hypertension and proteinuria developing after 20 weeks of gestation, is the cause of maternal and fetal deaths. The only definitive treatment currently available to save the mother and/or the baby is induced delivery. Anti-hypertensives acceptable for use during pregnancy help control maternal blood pressure in PE, but they do not prevent pre-term delivery nor correct the fetal growth restriction associated with PE. We have demonstrated that nicotinamide reduces the hypertension and proteinuria in mice having a pre-eclampsia-like condition, delays miscarriages and alleviates the fetal growth restriction. Nicotinamide is the first substance that benefits both mother and offspring by targeting a pathway specifically dysfunctional in PE. It merits evaluation for preventing or treating PE in humans.
NMR-based metabolimics research for epigenetic regulation by biotin in renal disease

TAKAHASHI SEIZO, FUJIWARA Masako, TAKAHASHI Nobuyuki, TAKEUCHI Kazuhisa

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Challenging Exploratory Research

Institution: Tohoku University

2012/04/01 - 2014/03/31

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We measured plasma biotin concentrations in hemodialysis patients by the ELISA method. The biotin concentrations in the patients were higher than that in the normal subjects. The ELISA detects all the molecules with biotin-backbone structures. The results indicated that renal disease patients without uric excretion accumulate biotin and biotin-metabolites in the blood. It was suggested the metabolites have no activity as vitamine, and disturb intact biotin. Chronic disease patients are affected seriously by the accumulated metabolites. For identification and quantification of biotin and the metabolites, we developed the LC/MS system. By NMR measurement of the plasma and spent dialysate samples from the patients, we study metabolic features special to chronic disease patients for the novel diagnosis.
Clarification of mechanism of renoprotective effect by renal oxygen metabolism and development of imaging method for renal function evaluation.

MORI Takefumi, ITO Sadayoshi, TAKAHASHI Nobuyuki, KANETA Tomohiro

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Challenging Exploratory Research

Institution: Tohoku University

2011 - 2012

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Hypoxia induced mitochondrial oxidative stress in renal medullary thick ascending limb of loop of Henle. Treatment with Mito-TEMPO significantly attenuated the reduction of renal medullary blood flow induced by ischemia/reperfusion. We established methods to evaluate renal function with [^<15>O]H_2O-PET and [^<18>F]FRP-170-PET. We created conditional prolyl hydroxylase (PHD) knockout mice, and measured the response of renal medullary blood flow in those mice. These results indicated that hypoxia could exacerbate renal injury though increase of mitochondrial oxidative stress and following reduction of renal medullary blood flow.
Role of coagulation factor 3 in diabetic nephropathy

TAKAHASHI Nobuyuki

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Research Activity Start-up

Institution: Tohoku University

2010 - 2011

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Diabetic nephropathy (DN)is the leading cause of end stage renal disease, and the number of patients with DN has been increasing rapidly. Human variants of the endothelial nitric oxide synthase gene (eNOS, NOS3)that produce reduced amounts of nitric oxide (NO)are positively associated with DN, although proof of causation is lacking. Here we have demonstrated that eNOS-/-mice with diabetes develop severe nephropathy. However, complete absence of eNOS has not been reported in humans, although reduced levels are not infrequent. Accordingly, heterozygous eNOS+/-mice have been made diabetic, and they demonstrated that the decrease in eNOS/NO comparable to that of NOS3 polymorphisms is sufficient to cause exacerbation of DN. Increased expression of tissue factor, initiator of coagulation, likely plays a significant role in the DN of the eNOS-/-diabetic mice. Strategies to ameliorate hypercoagulability could be useful for treatment of DN.

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Teaching Experience 16

病態解析学演習
ローテーション実習II
ローテーション実習I
医療薬学特別講義II
臨床薬学特別演習I
臨床薬学特別演習II
clinical pharmacology　Tohoku University
応用医療薬学特論　東北大学
薬学英語　東北大学
clinical statistics　Tohoku University
outline of clinical medicine　Tohoku University
clinical pharmacology　Tohoku University
basic seminar　Tohoku University
pharmaceutical therapeutics　Tohoku University
functional morphology　Tohoku University
大学大学院病理学　University of NorthCarolina at Chapel Hill

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