2022 Fiscal Year Final Research Report

Basic study on epithelial-mesenchymal transition leading to intractable fibrosis based on the somatic stem cells

Research Project

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Project/Area Number	19H03130
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Review Section	Basic Section 42020:Veterinary medical science-related
Research Institution	Osaka Metropolitan University (2022) Osaka Prefecture University (2019-2021)
Principal Investigator	Yamate Jyoji 大阪公立大学, 大学院獣医学研究科, 客員研究員 (50150115)
Co-Investigator(Kenkyū-buntansha)	桑村充大阪公立大学, 大学院獣医学研究科, 教授 (20244668) 井澤武史大阪公立大学, 大学院獣医学研究科, 准教授 (20580369)
Project Period (FY)	2019-04-01 – 2023-03-31
Keywords	線維化 / 筋線維芽細胞 / 臓器横断的 / 上皮‐間葉転換 / 体性幹細胞 / 幹細胞認識抗体 / ラット
Outline of Final Research Achievements	A novel antibody A3 recognized somatic stem cells capable of differentiating into both epithelial and mesenchymal cells. Using various antibodies in addition to A3, fibrotic lesions were induced in various organs of rats, and the characteristics of myofibroblasts were investigated based on the somatic stem cells. Along with undifferentiated mesenchymal cells and pericytes, myofibroblasts were generated from hepatic stellate cells, pancreatic stellate cells, and hair follicle connective tissue sheath cells as the organ-specific original cells. Epithelial-mesenchymal transition in injured renal tubules was involved in myofibroblast formation. These myofibroblast progenitors may be partly in the stem cell lineage. Macrophages involved in myofibroblast formation were induced in relationship to DAMPs and autophagy. This study contributes to the development of "stem cell pathology".
Free Research Field	獣医病理学
Academic Significance and Societal Importance of the Research Achievements	線維化は組織傷害後の修復機転である。線維化には膠原線維を産生する筋線維芽細胞が係る。筋線維芽細胞の特性と起源について体性幹細胞を起点に臓器横断的に追究した。特に、腎線維化では、傷害尿細管の遡及現象としての異常分化である上皮-間葉転換を介し筋線維芽細胞が形成される。また、ラットの体性幹細胞を認識する新たな抗体を作製し、その認識細胞の特性・分布を解析することで筋線維芽細胞の起源に新たな知見を加えた。また筋線維芽細胞の形成に係るマクロファージの誘導因子を障害関連分子パターン(DAMPs)とオートファジーとの係わりで検討した。この研究は「幹細胞病理学」の新たな構築と難治性線維化の治療法の探索に資する。