Exploring natriuretic peptide system-p38MAPK crosstalk in kidney injury

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K17739
• 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: MORI Keita P. 京都大学, 医学研究科, 客員研究員 (00769507)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 腎臓 / ナトリウム利尿ペプチド / p38 MAPK

Outline of Final Research Achievements

In this study, we focused on p38 MAPK (p38), which can act downstream of natriuretic peptide signaling in kidney injury, and CNP and its receptor Npr2, which are markedly upregulated in the kidney during renal injury, and aimed to clarify their significance and cross-talk in renal fibrosis.
We generated proximal tubule- and macrophage-specific p38-knockout (cKO) mice and induced UUO and ischemia-reflux models, but found no significant changes. Systemic drug-inducible Npr2-knockout mice (Npr2-cKO) were generated and renal Npr2 mRNA expression in these mice was successfully suppressed by almost 70%, but no significant changes were observed in UUO. Generation of double cKO of p38 and Npr2 was also attempted but not succeeded.

Free Research Field

腎臓内科学

Academic Significance and Societal Importance of the Research Achievements

我々の研究室では、p38がナトリウム利尿ペプチドシグナルの一つであるBNPとその受容体のNpr1(GC-A)の下流で腎糸球体の障害に寄与しうることを報告してきた。一方で、腎尿細管・間質におけるナトリウム利尿ペプチドの意義は十分明らかになっていない。腎障害時ではナトリウム利尿ペプチドの一つであるCNPやその受容体のNpr2(GC-B)の発現が著明に亢進することに着目し、これらの腎線維化での意義およびp38とのクロストークを明らかにすることを目標とした。
しかし、p38の近位尿細管や炎症細胞の一つのマクロファージにおける欠失や、Npr2の腎を含めた全身の欠失による腎線維化への影響は見いだせなかった。