Identification of muscle-derived cardioprotective miRNA

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08546
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Osaka City University
• Principal Investigator: Yoshiyama Minoru 大阪市立大学, 大学院医学研究科, 客員教授 (30240956)
• Co-Investigator(Kenkyū-buntansha): 泉家 康宏 大阪市立大学, 大学院医学研究科, 准教授 (10515414)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 骨格筋 / マイクロRNA / エクソソーム

Outline of Final Research Achievements

Skeletal muscle is recently recognized not only as a motor organ but also as an endocrine organ. In the present study, we attempted to identify muscle-derived exosomal miRNA that has cardiovascular protective properties. We comprehensively analyzed serum exosomal miRNA derived from skeletal muscle-specific Akt1 transgenic mice (muscular mice) and control mice by PCR Array. Among 641 miRNAs, 50 miRNAs were upregulated, and 56 miRNAs were downregulated in muscular mice. We found that miR206 and miR1a were upregulated in IGF1-stimulated hypertrophied myotubes. Exogenous supplementation of miR206 showed angiogenic properties in vitro endothelial cells. These results suggest that muscle-derived miR206 act as a pro-angiogenic factor in response to muscle hypertrophy.

Free Research Field

循環器内科

Academic Significance and Societal Importance of the Research Achievements

心血管疾患患者に対する運動療法の有用性は確立し,臨床の現場においても心臓リハビリテーションとして広く普及してきているが,その有用性の分子機序は不明な点が多く残されている.運動により骨格筋から臓器保護的なホルモンが分泌され遠隔臓器に作用するというコンセプトを我々はこれまで様々なデータとして報告してきた.本研究で同定された骨格筋由来のエクソソームに内包され分泌されるマイクロRNAの同定は,そのコンセプトをさらに推し進めるものと考えられる.骨格筋から分泌されるマイクロRNAの更なる機能解析が今後の治療応用につながると考えられる.