Elucidation of Rennal Metabolic Regulation Mechanisms by Transcription Factor MondoA

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K16240
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Osaka University
• Principal Investigator: Sakai Shinsuke 大阪大学, 医学部附属病院, 医員 (60817360)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: オートファジー / 解糖系 / 代謝

Outline of Final Research Achievements

We extensively investigated the metabolic control mechanism of transcription factor MondoA in renal constituent cells. Examination of the renal tissue distribution of MondoA protein revealed significant staining in the cortex, with lower staining observed in the medulla and glomeruli. Evaluation of Podocyte-specific MondoA-deficient mice (KO mice) did not show significant histological changes in young, aged, or diabetic models; however, changes were observed in glycolytic metabolism intermediates such as Pyruvate and Lactate in isolated glomeruli. Evaluation of tubular cells in similar models did not reveal histological changes, but there was a significant decrease in autophagic flux and changes in glycolytic metabolism intermediates. This was crucial for tubular protection during ischemia-reperfusion injury.

Free Research Field

代謝

Academic Significance and Societal Importance of the Research Achievements

MondoAはオートファジーを制御する転写因子として注目されているが、腎組織において詳細な検討を行ったものは初めてである。Podocyteおよび近位尿細管ともにMondoAは解糖系を制御することが明らかになったが、予想に反して解糖系代謝の低い近位尿細管でのMondoAの分子機構が、腎傷害やオートファジー活性につながり、CKDへの進行に深くかかわることが明らかになった。老化において発現変動する蛋白であることから、腎不全の進展を抑制を抑制する新たなターゲット分子として寄与する可能性がある。