Clarifiation of CKD progression by regulating fibrotic microenvironment

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08605
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Kanazawa University
• Principal Investigator: SAKAI NORIHIKO 金沢大学, 附属病院, 准教授 (60377421)
• Co-Investigator(Kenkyū-buntansha): 和田 隆志 金沢大学, その他部局等, その他 (40334784)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 線維化 / 線維芽細胞 / 接着斑

Outline of Final Research Achievements

Fibrosis is characterized by an excessive wound healing response to organ damage, causing extracellular matrix deposition and accumulation of fibroblasts/myofibroblasts. In the process of enal failure, various renal diseases are characterized by taking a common process which is renal fibrosis. In this study, we attempted to elucidate the significance of cytoskeleton-dependent signal for renal fibrosis by regulating the biological properties of renal fibroblasts. As a result, it was revealed that the cytoskeleton-dependent MRTF-SRF signal by TGF-b1 in renal fibroblasts contributes to the expression of focal adhesion components and extracellular matrix such as colalgen and fibronectin. In addition, systemic MRTF-A- and fbroblast-specific MRTF-B- deficiency attenuates renal fibrosis by inhibiting the expression of focal adhesion components and extracellular matrix. Tese results suggest that MRTF-SRF signaling in fibroblast might be a target to combat renal fibrosis.

Free Research Field

腎臓内科学

Academic Significance and Societal Importance of the Research Achievements

本研究では、細胞骨格に関連するMRTF-SRFシグナルが、腎臓を構成する線維芽細胞機能を調節することで腎不全の原因となる線維化に関与するかを試みた。その結果、腎線維芽細胞において、MRTF-SRFシグナルが、腎線維芽細胞を活性化させ、腎線維化進展に寄与することを明らかにした。これは腎障害の原因に関わらない共通進展機序であり、現在増加の一途を辿っている末期腎不全患者数の抑制につながる新規治療法開発につながることが期待される。