Analysis of the role of mesenchymal stem cell marker Meflin in kidney fibrosis

Research Project

Project/Area Number	17K09696
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Kidney internal medicine
Research Institution	Nagoya University
Principal Investigator	Saito Shoji 名古屋大学, 医学部附属病院, 助教 (00635609)
Co-Investigator(Kenkyū-buntansha)	丸山彰一名古屋大学, 医学系研究科, 教授 (10362253) 榎本篤名古屋大学, 医学系研究科, 准教授 (20432255) 坪井直毅藤田医科大学, 医学部, 准教授 (50566958)
Project Period (FY)	2017-04-01 – 2020-03-31
Project Status	Completed (Fiscal Year 2019)
Budget Amount *help	¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000) Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000) Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords	腎線維化 / 間葉系幹細胞 / 線維化
Outline of Final Research Achievements	Fibrosis is a key regulator of organ damage.myofibroblast is essential for rise of fibrosis, and it is said that MSC is one of the origin. We previously report that a cell surface and secreted protein, Meflin, is expressed in cultured MSCs, fibroblasts and pericytes, but not other types of cells including epithelial, endothelial and smooth muscle cells. We also found Meflin is a potential marker for cultured MSCs and focused on the mechanism of fibrosis by investigating Meflin. We discovered that Meflin expresses in intersititum and around the vascular pole of glomerulus. And its’ expression increases when glomerular inflammation and fibrosis progresses.We also investigated the manner of Meflin positive cells with Meflin reporter mice generated in our lab. In vitro study also suggested that Meflin is positively regulating kidney fibrosis.
Academic Significance and Societal Importance of the Research Achievements	MSCは近年、細胞治療や再生医療の分野で注目される細胞である。MSCは炎症集積性を有する細胞であり、さらには筋線維芽細胞のソースであることから、線維化疾患の理解においてMSCの理解は必須である。Meflinは私達が知る限り未分化MSCの最も特異的なマーカーであり、MSCの研究において今後非常に有用なマーカーとなると推察される。 Meflinの機能解析を基軸にして、腎線維化の機序解明をする研究である。線維化は慢性腎臓病のみならず、心不全、肝硬変、肺線維症、癌と多様な疾患の病態理解に必須であることから、その医学への貢献は高く評価されるものと期待している。