The Role of Metabolic Reprogramming-Induced Cell Differentiation in the Development of Pulmonary Fibrosis

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08560
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: University of Tsukuba
• Principal Investigator: Matsuno Yosuke 筑波大学, 医学医療系, 講師 (30633177)
• Co-Investigator(Kenkyū-buntansha): 石井 幸雄 筑波大学, 医学医療系, 教授 (80272194)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 肺線維症 / ミトコンドリア / 線維芽細胞

Outline of Final Research Achievements

Mitochondria plays a crucial role in regulating intracellular metabolism, and loss of mitochondrial function has a profound effect on cell function by altering metabolic pathways. We conducted this study to elucidate the role of mitochondria in lung fibrosis using mito-mice with impaired mitochondrial function due to mutations in the mitochondrial genome. Lung fibrosis induced by bleomycin was enhanced in Mito mice. In lung fibroblasts from Mito mice, TGF-β1-induced differentiation into myofibroblasts was enhanced, accompanied by activation of metabolic pathways required for collagen biosynthesis. Mitochondria may contribute to the development of lung fibrosis by inducing metabolic reprogramming and pathological differentiation in fibroblast.

Free Research Field

びまん性肺疾患

Academic Significance and Societal Importance of the Research Achievements

これまで、肺線維化の病態においては、ミトコンドリアの機能障害を含め、様々な老化と関連した細胞形質の存在が知られていたが、ミトコンドリアが肺線維化で担う独自の役割は不明であった。本研究はミトマウスを用いることにより、ミトコンドリア機能障害が、単独で肺の線維化進展に寄与すること、線維化と関連した線維芽細胞の分化を誘導すること、を初めて明らかにした。本研究を礎として、ミトコンドリアを標的とした肺線維症の新たな診断・治療方法の開発が進展することが期待される。