Involvement of epimorphin in the repair of peritoneal fibrosis model in mice

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09739
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Tokyo Medical University
• Principal Investigator: Yamada Muneharu 東京医科大学, 医学部, 講師 (10625164)
• Co-Investigator(Kenkyū-buntansha): 平井 洋平 関西学院大学, 理工学部, 教授 (00397572) ; 尾田 高志 東京医科大学, 医学部, 教授 (90531187)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 腹膜透析 / エピモルフィン / 腹膜線維化

Outline of Final Research Achievements

Long‐term peritoneal dialysis (PD) is accompanied by functional and histopathological alterations in the peritoneal membrane, leading to peritoneal fibrosis (PF) that results in discontinuation of PD. Mechanism of PF remains to be fully elucidated and there is no effective therapy available. Epimorphin is a mesenchymal protein that not only regulates morphogenesis in organ development but is implicated in tissue repair. We found weak expression of epimorphin in submesothelial compact zone (SCZ) in normal mice peritoneum. The epimorphin expression, however, was stronger in SCZ in chlorhexidine gluconate-induced peritoneal fibrosis model in mice. Furthermore, we found that epimorphin suppressed the TGF-β1-induced upregulation of α-smooth muscle actin and platelet-derived growth factor receptor-β, which were the pro-fibrotic phenotypic markers, in rat fibroblast cells in vitro. Taken together, epimorphin might be a therapeutic target for fibrotic diseases of the peritoneum.

Free Research Field

腎臓内科

Academic Significance and Societal Importance of the Research Achievements

腹膜透析は残腎機能の保持に優れた非常に有用な腎代替療法であるが、長期継続により腹膜機能が低下し血液透析に移行せざるを得ない。本研究によってエピモルフィンが腹膜保護作用を持つ可能性が示され、今後さらに液性因子等の詳細な機序を検討することにより、腹膜線維症に対する早期からの治療介入や腹膜線維化に対する新規治療となる可能性が期待される。