Regulatory mechanism and pathophysiological implication of MR-pendrin pathway by renin-angiotensin-aldosterone system

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K16074
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Kidney internal medicine
• Research Institution: The University of Tokyo
• 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)
• Project Period (FY): 2017-04-01 – 2019-03-31
• 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

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.

Free Research Field

腎臓内科学、高血圧学

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。