ROCK1 activation induces mesangial damage in diabetes

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K15985
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Jikei University School of Medicine
• Principal Investigator: Matoba Keiichiro 東京慈恵会医科大学, 医学部, 講師 (20459647)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 糖尿病腎症 / 糖尿病 / 慢性腎臓病 / Rho-kinase / ROCK1 / エネルギー代謝

Outline of Final Research Achievements

Given the worldwide increase in diabetes and end-stage renal disease, with increased risk of death, there is a pressing need to stop the progression of renal dysfunction. Although efforts have been made to develop medications for chronic kidney disease (CKD) in patients with diabetes, there still remains a high residual risk for CKD progression and cardiovascular mortality. The present study identifies ROCK1 as a critical regulator of glomerular metabolism in diabetes. Specifically, we show that ROCK1-deficient mice are protected from albuminuria and mesangial expansion in type 2 diabetes model. Mechanistically, our studies suggest that ROCK1 regulates fatty acid utilization and redox homeostasis. When considered alongside previous reports demonstrating pathogenic roles of ROCK1 in other renal cells, these observations identify ROCK1 as a promising therapeutic target against CKD in patients with diabetes.

Free Research Field

糖尿病腎症

Academic Significance and Societal Importance of the Research Achievements

糖尿病腎症に対するこれまでの治療は、糖尿病や高血圧などのリスク因子管理が主体であり、病態に直接アプローチする方法が存在しなかった。本研究成果は、ROCK1が糖尿病腎症の糸球体エネルギー代謝異常に強く関与することを示唆しており、新たな創薬ターゲットとして期待される。