Investigation of molecular mechanisms involved in the pathogenesis of muscular contracture and development of physical therapeutic strategies

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K19795
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 59010:Rehabilitation science-related
• Research Institution: Nagasaki University
• Principal Investigator: HONDA Yuichiro 長崎大学, 医歯薬学総合研究科(保健学科), 助教 (40736344)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 筋性拘縮 / 線維化 / アポトーシス / ミトコンドリア / mfn-1 / drp-1

Outline of Final Research Achievements

Our laboratory clarified that myonuclear apoptosis was related to the development of muscle fibrosis, which was the main lesion of muscle contracture. However, the upstream of this mechanism was unclarified. whereas, previous research indicated that mitochondrial dysfunction has affected the incidence of apoptosis. Also, the reduction of mitochondria DNA through the downregulation of mitofusin (mfn)-1 expression and the upregulation of dynamin-related protein (drp)-1 expression was associated with the decrease in mitochondrial membrane potential, these alterations induced apoptosis via mitochondrial dysfunction. Accordingly, we hypothesize similar alterations trigger myonuclear apoptosis in immobilized skeletal muscle, examined the above hypothesis in this study. As a result, we confirmed the alterations similar to the hypothesis in the immobilized skeletal muscle. Namely, these changes induced myonuclear apoptosis and led to the development of muscle contracture via muscle fibrosis.

Free Research Field

理学療法学

Academic Significance and Societal Importance of the Research Achievements

本研究成果とこれまでの自験例を照合した結果，不動状態に曝された骨格筋ではmfn-1の発現低下とdrp-1の発現亢進に伴うミトコンドリアDNAの減少によってミトコンドリア膜電位が低下し，これらの変化が筋核のアポトーシスを誘発することで線維化が生じることが明らかとなった．そして，この成果は筋性拘縮の発生メカニズムを解明するための一助になるものであり，これを応用すれば生物学的なエビデンスに裏打ちされた筋性拘縮に対する理学療法学的戦略の開発につながると考えられる．