| 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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