Elucidation of a novel hypertension mechanism mediated by myosin phosphate

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K15678
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 42020:Veterinary medical science-related
• Research Institution: The University of Tokyo
• Principal Investigator: Yang Qunhui 東京大学, 大学院農学生命科学研究科(農学部), 特任研究員 (10866924)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 高血圧 / CPI-17 / DOCA-食塩

Outline of Final Research Achievements

In this study, we focused on the pathophysiological function of CPI-17, a protein essential for maintaining normal blood pressure, and analyzed the function of CPI-17 in deoxycorticosterone acetate-salt (DOCA-salt)-induced hypertension using CPI-17 gene-modified mice. mice and [T38A]CPI-17 knock-in mice significantly reduced DOCA model-induced hypertension, indicating that the phosphorylation signal of Thr38 in CPI-17 plays an important role in the development of salt-loaded hypertension. These findings lead to the discovery of new therapeutic targets and are extremely important in clinical medicine.

Free Research Field

獣医薬理

Academic Significance and Societal Importance of the Research Achievements

食塩誘発性の高血圧は日本では古くから臨床上問題となっている. 近年、RhoA/Rhoキナーゼ/MYPT1リン酸化経路がこの高血圧発症に重要な役割を担うことが明らかにされたが、Rho/Rhoキナーゼと並んで、ミオシンホスファターゼを阻害するPKCあるいはRhoA/RhoキナーゼCPI-17経路の関与は不明であった。本研究により新たにCPI-17経路も食塩誘発高血圧発症に関与する可能性が示されたことは、臨床医学上きわめて重要な知見である。