Exploration of gluco- and mineralocorticoid-dependent sodium transporter system involved in salt sensitive hypertension
| Project/Area Number |
16K15494
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Endocrinology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Fujita Toshiro 東京大学, 先端科学技術研究センター, 特任研究員 (10114125)
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| Co-Investigator(Kenkyū-buntansha) |
鮎澤 信宏 東京大学, 先端科学技術研究センター, 特任研究員 (50459517)
丸茂 丈史 東京大学, 医学部附属病院, その他 (70265817)
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 食塩感受性高血圧 / ミネラルコルチコイド / 遠位尿細管 / 鉱質コルチコイド受容体 / ペンドリン / 高血圧 / 酸塩基異常 / 内科 |
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| Outline of Final Research Achievements |
Pendrin is expressed in intercalated cells of the renal tubules and plays a pivotal role in maintenance of body fluid and blood pressure. The present study revealed the essential role of aldosterone-mineralocorticoid receptor (MR) pathway in the activation of pendrin by angiotensin II using adrenalectomy model and MR knockout mice, paving the way to the development of new therapy against salt-sensitive hypertension.
Apparent mineralocorticoid excess (APE) is caused by mutations in the HSD11B2 gene, which lead to hypertension. To delineate the role of the kidney, we generated mice with kidney-specific deletion of HSD11B2. These mice developed hypertension, along with activation of epithelial sodium channel-Na+-Cl- cotransporter activation. Mineralocorticoid receptor antagonist decreased blood pressure of the knockout mice. These results suggest the importance of 11beta HSD2 expressed in the kidney in MR activation and development of hypertension in APE syndrome.
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Report
(3 results)
Research Products
(26 results)
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[Journal Article] Aberrant DNA methylation of pregnane X receptor underlies metabolic gene alterations in the diabetic kidney2018
Author(s)
Uchida K, Tanaka Y, Ichikawa H, Watanabe M, Mitani S, Morita K, Fujii H, Ishikawa M, Yoshino G, Okinaga H, Nagae G, Aburatani H, Ikeda Y, Susa T, Tamamori-Adachi M, Fukusato T, Uozaki H, Okazaki T, Iizuka M
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Journal Title
American Journal of Physiology-Renal Physiology
Volume: 314
Issue: 4
Pages: F551-F560
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Renal dysfunction induced by kidney-specific gene deletion of Hsd11b2 as a primary cause of salt-dependent hypertension2017
Author(s)
Kohei Ueda, Mitsuhiro Nishimoto, Daigoro Hirohama, Nobuhiro Ayuzawa, Wakako Kawarazaki, Atsushi Watanabe, Tatsuo Shimosawa, Johannes Loffing, Ming-Zhi Zhang, Takeshi Marumo, and Toshiro Fujita
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Journal Title
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Effect of mineralocorticoid receptor antagonists on proteinuria and progression of chronic kidney disease: a systematic review and meta-analysis.2016
Author(s)
Currie G, Taylor AH, Fujita T, Ohtsu H, Lindhardt M, Rossing P, Boesby L, Edwards NC, Ferro CJ, Townend JN, van den Meiracker AH, Saklayen MG, Oveisi S, Jardine AG, Delles C, Preiss DJ, Mark PB.
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Journal Title
BMC Nephrol.
Volume: 17
Issue: 1
Pages: 127-140
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Systemic effect of renal 11beta-HSD2 deficiency on blood pressure regulation2017
Author(s)
Kohei Ueda, Mitsuhiro Nishimoto, Daigoro Hirohama, Nobuhiro Ayuzawa, Wakako Kawarazaki, Atsushi Watanabe, Tatsuo Shimosawa, Johannes Loffing, Ming-Zhi Zhang, Takeshi Marumo, Toshiro Fujita
Organizer
AHA Council on Hypertension American Society of Hypertension Joint Scientific Sessions
Related Report
Int'l Joint Research
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