2022 Fiscal Year Final Research Report
Analysis of the mechanism and role of mineralocorticoid receptor-mediated regulation of pendrin
Project/Area Number |
20K08585
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 53040:Nephrology-related
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Research Institution | Kyorin University (2022) The University of Tokyo (2020-2021) |
Principal Investigator |
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Keywords | pendrin / ミネラロコルチコイド受容体 / アルドステロン / 高血圧 / 尿細管 |
Outline of Final Research Achievements |
NaCl reabsorption in the distal nephron is involved in the development of hypertension. Recently, it was reported that pendrin, expressed in beta-intercalated cells in cortical collecting ducts, is involved in NaCl reabsorption and elevation of blood pressure. In the present study, we found that pendrin is up-regulated by two distinct pathways via mineralocorticoid receptor (MR) during activation of the renin-angiotensin-aldosterone system, which contributed to fluid retention and blood pressure elevation. We also showed that these pathways act to maintain hypertension, especially during thiazide diuretic treatment, resultantly forming treatment-resistant pathologies.
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Free Research Field |
腎臓、高血圧
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Academic Significance and Societal Importance of the Research Achievements |
本研究により解明されたRAAS亢進時における2つの異なるMRを介したpendrin制御機構は、高血圧性病態、特にサイアザイド利尿薬による治療に抵抗性の病態において、新規の治療標的となる可能性が示された。これら病態において、MR拮抗薬は、2つのpendrin制御機構の両方を抑制する効果的な治療戦略になることが示唆される。また、今後これらpendrin制御機構のさらなる詳細な解明により、新たな治療標的の創出も期待される。
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