Elucidation of the resistant gene program against muscle atrophy in skeletal muscle cells

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K22815
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 59:Sports sciences, physical education, health sciences, and related fields
• Research Institution: Osaka Metropolitan University (2022-2023); Osaka Prefecture University (2019-2021)
• Principal Investigator: KONDO Shigetada 大阪公立大学, 大学院生活科学研究科, 教授 (40304513)
• Project Period (FY): 2019-06-28 – 2024-03-31
• Keywords: 骨格筋細胞 / 廃用性筋萎縮 / 萎縮ストレス

Outline of Final Research Achievements

In this study, we clarified the adaptive mechanism of skeletal muscle cells (myotubes) against muscle atrophy stress. We identified the skeletal muscle-specific novel long non-coding RNA (Irs1 lncRNA). We demonstrated that the target mRNAs of Irs1 lncRNA are RB and p16. Furthermore, we found that Irs1 lncRNA silences these target mRNAs through complementary sequences, resulting in the dedifferentiation of myotube cells and the acquisition of a phenotype resistant to muscle atrophy stress. Furthermore, we investigated the transcriptional regulatory mechanism of Irs1 lncRNA and the host gene (Irs1 mRNA), and revealed that these two RNAs are transcriptionally regulated in a stage-specific manner in muscle cell differentiation.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

現在、廃用性筋萎縮を引き起こすメカニズムについては、筋特異的な蛋白質分解システムの活性化(Atrogenesシステム)が国内外で精力的に研究され、分子レベルでその詳細が明らかにされてきている。一方、筋細胞がもつ「萎縮ストレスに対する適応能力」という観点から、筋萎縮を捉えた研究は未だない。本研究成果の学術的意義は、骨格筋細胞に備わった筋萎縮抵抗性プログラムを明らかにし、廃用性筋萎縮の解決へ向けた新たな可能性を示したことである。