Development of novel therapy for diabetic nephropathy using lipid metabolism

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08245
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Tohoku University
• Principal Investigator: Toyohara Takafumi 東北大学, 大学病院, 准教授 (60594182)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 糖尿病性腎臓病

Outline of Final Research Achievements

We investigated the role of Arylamide Deacetylase (AADAC) in lipid toxicity and the function of each kidney constituent cell in diabetic nephropathy. As for in vivo studies, while Aadac knockout mice exhibited different insulin responsiveness, no differences were observed in the Glucose Tolerance Test (GTT), suggesting that AADAC may be involved in insulin sensitivity. Additionally, a comparison of endothelial cells differentiated from iPS cells of patients susceptible and not susceptible to diabetic nephropathy revealed that endothelial cells derived from patients susceptible to diabetic nephropathy showed increased expression of genes related to apoptosis, inflammatory responses, and reactive oxygen species.

Free Research Field

腎臓内科学

Academic Significance and Societal Importance of the Research Achievements

糖尿病性腎症は透析導入原因疾患の第一位であるが、血圧と血糖のコントロールのみの治療では不十分であり病態解明や有効な治療法の開発が急務である。糖尿病や肥満においては全身臓器の細胞内に脂肪が蓄積し、いわゆる‘脂肪毒性’を引き起こす。糖尿病性腎症においても腎臓の構成細胞（内皮細胞、糸球体足細胞、近位尿細管）が脂質を始めとした変化を示し病態に関与することが知られている。本研究ではAADACという小胞体リパーゼの糖尿病における働きを解析し、糖尿病性腎臓病における腎臓構成細胞の役割の一端を解明した。今後の糖尿病性腎臓病に対する治療の重要な基礎になると考えられる。