Role of protein O-GlcNAcylation in pathogenesis of diabetic kidney disease

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08724
• 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: Shiga University of Medical Science
• Principal Investigator: Kanasaki Masami 滋賀医科大学, 医学部, 講師 (30402720)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 腎臓病 / 糖鎖修飾 / 糖尿病性腎症 / 肥満関連腎臓病

Outline of Final Research Achievements

The increasing prevalence of obesity-related kidney disease and diabetic nephropathy due to the increasing number of obese patients is one of the most pressing issues in Japan that must be resolved. In this study, we investigated the physiological role of O-GlcNAcylation, one of the post-translational modifications of proteins, in the kidney and whether its regulation could be a new therapeutic target for kidney disease. The results revealed that the O-GlcNAcylation is essential for ATP production via fatty acid burning during fasting in renal proximal tubular cells, and that its abnormalities contribute to the pathogenesis of renal injury in obesity and diabetic conditions.

Free Research Field

腎臓病

Academic Significance and Societal Importance of the Research Achievements

肥満患者数の増加に伴う腎臓病患者数の増加に対する新たな治療法が求められている。本研究では、腎臓におけるO-GlcNac修飾が腎臓におけるエネルギー代謝の中枢を担うメカニズムであり、その異常が肥満や糖尿病を背景とする腎臓病の発症進展に寄与することが明らとなった。今後の研究の発展により、O-GlcNac修飾を標的とした新規腎臓病治療の開発が期待される。