Structure-function association in podocytopathy via Rho family small G proteins

2015 Fiscal Year Final Research Report

• Project/Area Number: 26670427
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Kidney internal medicine
• Research Institution: Juntendo University
• Principal Investigator: Nagase Miki 順天堂大学, 医学(系)研究科(研究院), 准教授 (60302733)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: ポドサイト傷害 / Rac1 / アクチン細胞骨格 / 細胞の運動性 / 低分子量G蛋白質 / 鉱質コルチコイド受容体 / マクロファージ / 心筋細胞

Outline of Final Research Achievements

Rac1, a Rho family small GTPase, is a multi-functional molecule that controls cytoskeleton, oxidative stress, gene transcription, and cell motility, in a cell-specific manner. In this study, we analyzed the role of Rac1 in the pathobiology of glomerular podocytes, focusing on the structure-function association, and compared its roles in other cells. In podocytes, both Rac1 hyperactivation and hypoactivation resulted in podocyte injury, albuminuria, and glomerulosclerosis, and affected actin cytoskeleton and cell motility by distinct mechanisms. Macrophage Rac1 played a central role in lipopolysaccharide-evoked acute kidney injury through M1 cytokine production. Cardiomyocyte Rac1 contributed to the pressure overload-induced heart failure via induction of NOX4.

Free Research Field

腎臓内科学