Role of p38MAPK on podocyte in aldosterone- induced glomerular injury

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K17246
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Kyoto University
• Principal Investigator: Kato Yukiko 京都大学, 医学研究科, 研究員 (40769519)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: ポドサイト / アルドステロン / ナトリウム利尿ペプチド / p38 MAPK / ノックアウトマウス

Outline of Final Research Achievements

The role of p38MAPK and natriuretic peptide receptor A (GC-A) in aldosterone-induced podocyte injury was investigated. To investigate the significance of p38MAPK in podocytes, podocyte-specific GC-A & p38αMAPK double knockout mice were generated and subjected to aldosterone and high salt diet. The double-knockout mice showed severe albuminuria and marked podocyte damage. In addition, the mice showed fibrin thrombi in the capillary lesion and endothelial damage. Using cultured human podocyte with MAPK14 deletion GC-A knockdown, we showed that decreased p38MAPK and GC-A in podocytes is involved in the upregulation of gene expression related to the extracellular matrix of endothelial cells.

Free Research Field

腎臓内科学

Academic Significance and Societal Importance of the Research Achievements

ポドサイトのGC-Aとp38 MAPKの意義を検討するために、ポドサイト特異的GC-A＆p38MAPKダブルノックアウトマウスを作製し、これら2つの因子が特に高食塩負荷時・アルドステロン過剰状態において、糸球体障害を増悪させることを示した。社会的意義として、高血圧ならびに高食塩時の腎障害の機序解明に貢献している。