Regulatory mechanism and pathophysiological implication of MR-pendrin pathway by renin-angiotensin-aldosterone system
| Project/Area Number |
17K16074
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Kidney internal medicine
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Hirohama Daigoro 東京大学, 先端科学技術研究センター, 特任研究員 (20749353)
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | Pendrin / アンジオテンシンII / アルドステロン / 鉱質コルチコイド受容体 / MR / 間在細胞 / 塩分欠乏 / 血圧 / 食塩欠乏 / pendrin / angiotensin / aldosterone |
|---|
| Outline of Final Research Achievements |
Although it has been proposed that the mineralocorticoid receptor-pendrin system in intercalated cells of the renal tubules is involved in the NaCl reabsorption, its regulatory mechanism and pathophysiological implication in vivo remained unclear.
In this study using low-salt diet-treated mice or adrenalectomized mice, we demonstrated that both angiotensin II and aldosterone are indispensable for pendrin activation during salt depletion, and that both have synergistic effects. We revealed that pendrin contributes to maintenance of normal blood pressure during the renin-angiotensin-aldosterone system activation with a low-salt diet, using pendrin-knockout mice. Moreover, we revealed that in primary aldosteronism with salt repletion, pendrin plays an important role to prevent hypokalemia.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は体液ホメオスターシスと血圧制御の機構においてpendrinの役割の重要性を指摘した。これはpendrinの異常活性化が食塩感受性高血圧を発症させうることだけでなく、pendrin阻害剤が新たな高血圧治療薬となりうることも示唆している。
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Report
(3 results)
Research Products
(29 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)
Ueda K, Nishimoto M, Hirohama D, Ayuzawa N, Kawarazaki W, Watanabe A, Shimosawa T, Loffing J, Zhang MZ, Marumo T, Fujita T
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Journal Title
Hypertension
Volume: 70
Issue: 1
Pages: 111-118
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] 腎臓特異的DNAメチル化を尿中マーカーとした糖尿病性腎症の尿細管障害診断法2018
Author(s)
丸茂 丈史, 下澤 達雄, 河原崎 和歌子, 西本 光宏, 鮎澤 信宏, 広浜 大五郎, 上田 浩平, 佐藤 敦久, 渥美 義仁, 星野 純一, 乳原 善文, 藤田 敏郎
Organizer
第61回日本腎臓学会学術総会
Related Report
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[Presentation] 特異的DNAメチル化マーカーを用いた糖尿病性腎症の尿細管障害診断2017
Author(s)
丸茂 丈史, 下澤 達雄, 河原崎 和歌子, 西本 光宏, 鮎澤 信宏, 広浜 大五郎, 上田 浩平, 渡邉 篤史, 星野 純一, 乳原 善文, 藤田 敏郎
Organizer
第60回日本腎臓学会学術総会
Related Report
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