Association of p38 MAPK with natriuretic peptide receptors in renal glomeruli

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K16188
• 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: Yamada Hiroyuki 京都大学, 医学研究科, 助教 (70713650)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: ポドサイト / ナトリウム利尿ペプチド / p38 MAPK / ANP

Outline of Final Research Achievements

This study focused on the functions of natriuretic peptide (Guanylyl cyclase-A; GC-A) and p38 MAPK in glomerular podocytes. Podocyte-specific GC-A & p38 MAPK double knockout mice showed podocyte damage and thrombi in the glomerular coxae.
Next, when GC-A expression was decreased in p38 MAPK knockout cultured podocytes, the expression of inflammatory cytokines elevated. Moreover, it also increased the expression of TGF-β and FN in co-cultured human umbilical vein endothelial cells.
These results suggest that deletion at p38 MAPK and GC-A in podocytes causes damage in podocytes and vascular endothelial cells.

Free Research Field

腎臓

Academic Significance and Societal Importance of the Research Achievements

今回の研究により、p38 MAPKが糸球体のポドサイトと血管の血管内皮細胞のそれぞれとの関連性において非常に重要なタンパク質であることが明らかになった。また、これまでヒト培養ポドサイトにおいてゲノム編集技術の応用が成功した例は少なく、本技術がポドサイトに応用可能であることがわかり、今後の研究の発展性を大きく広げた。