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2022 Fiscal Year Final Research Report

An investigation of novel therapeutic strategy for diabetic nephropathy based on control of mitochondrial turnover

Research Project

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Project/Area Number 20K08609
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53040:Nephrology-related
Research InstitutionThe University of Tokushima

Principal Investigator

TAMAKI Masanori  徳島大学, 病院, 講師 (90528902)

Project Period (FY) 2020-04-01 – 2023-03-31
Keywords糖尿病性腎症 / ミトコンドリア / Parkin / BMP4
Outline of Final Research Achievements

The role of parkin on diabetic nephropathy was analyzed. Mitochondrial dysfunction was caused in streptozotocin induced diabetic mice, associated with decrease in parkin and PGC-1α expression. Similar findings were observed in mice treated with BMP4-continuous administration by use of osmotic pump. Mitochondrial dysfunction was observed in BMP4-treated cultured mesangial cells associated with decrease in parkin and PGC-1α expression. In parkin-knock down cultured mesangial cells, decrease in PGC-1α expression and mitochondrial dysfunction was observed. Conversely, mitochondrial dysfunction and decrease in parkin and PGC-1α expression after treatment with BMP4 were attenuated in parkin-overexpressed cultured mesangial cells. These findings indicated that BMP4 caused mitochondrial dysfunction which was similar to diabetic mice, and parkin was suggested as a new therapeutic target for mitochondrial dysfunction.

Free Research Field

腎臓内科学

Academic Significance and Societal Importance of the Research Achievements

糖尿病性腎症では腎ミトコンドリア機能低下が惹起される。ミトコンドリアの品質管理はミトコンドリア生合成・マイトファジーで制御されるターンオーバーでなされるが、糖尿病性腎症におけるミトコンドリアターンオーバーの意義解明は不十分であり、特に糖尿病性腎症における主要なメサンギウム基質増加因子である骨形成因子4(BMP4)との関連は不明であった。本研究を通じて、糖尿病性腎症ではマイトファジー鍵分子Parkinの発現低下に関連したマイトファジー障害とミトコンドリア生合成障害の両者が惹起され、BMP4も同様の作用を示すことが明らかとなった。BMP4やParkinが治療標的となり得ることが示された。

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Published: 2024-01-30  

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