A new role of calpain in myocardial infarction

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K10558
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 58040:Forensics medicine-related
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Shintani-Ishida Kaori (石田香) 京都府立医科大学, 医学(系)研究科(研究院), 准教授 (50345047)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: miRNA / 筋肉 / 分化 / 加齢

Outline of Final Research Achievements

Calpain, a protease, breaks down functional and structural proteins and mediates diseases including myocardial infarction. miRNAs are involved in post-transcriptional regulation. This study found a new role of calpain: calpain regulates muscle-specific miRNA expression. In C2C12 mouse myoblasts, calpain inhibition or cell senescence downregulated miR-133a and miR-1 expression and suppressed myogenic differentiation. Overexpression of miR-133a and/or miR-1 ameliorated the differentiation. In addition, primary cultured myoblasts prepared from aged mice exhibited a decrease in miR-1 and miR-133a levels compared with younger mice.

Free Research Field

法医学

Academic Significance and Societal Importance of the Research Achievements

筋特異的miRNAの発現を調節するというカルパインの新しい役割が見出された。さらに、筋特異的miRNAは加齢によっても発現が抑制され、筋芽細胞の筋分化能を低下させることが明らかになった。筋肉が損傷を受けると筋幹細胞が活性化し、筋芽細胞となって分化し、筋管細胞を形成し、損傷部位を再生する。本研究成果は、心筋梗塞後の心筋傷害だけでなく、高齢者に見られる骨格筋萎縮（加齢性筋肉減弱症）にも関係していると考えられる。