Investigation of skeletal muscle atrophy mechanism and role of microRNA using human iPS cells

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K17814
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General pharmacology; Metabolomics
• Research Institution: Shiga University of Medical Science
• Principal Investigator: Iwasaki Hirotaka 滋賀医科大学, 医学部, 助教 (40781589)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 骨格筋 / 筋分化 / miRNA

Outline of Final Research Achievements

The purpose of this study is to investigate how miR-494, which regulates muscle fiber type formation, plays a role in vivo. and to develop therapeutic agents for lifestyle-related diseases and muscle diseases.
First, we found that miR-494 directly controls p300 and regulates type IIa muscle fiber formation during myogenesis from human iPS cells. p300 is involved in muscular dystrophy development, suggesting that miR-494 may be included in the pathology of muscle disease. Second, we found that miR-494 suppressed p300 and Myh2 expression in mouse skeletal muscle. We also succeeded in producing miR-494 knockout mice.
This result suggests that miR-494 may be a target for the treatment of muscle diseases.

Free Research Field

薬理学

Academic Significance and Societal Importance of the Research Achievements

我が国は、超高齢化社会を迎えており、筋骨格系の機能を維持しながら、健康に老いる事が重要になっている。骨格筋は代謝特性の異なるⅠ型、Ⅱa型およびⅡx型筋線維から構成されるが、2型糖尿病ではⅠ型、Ⅱa型筋線維が萎縮しやすく、サルコペニアや加齢ではⅡx型筋線維が萎縮しやすいことが近年明らかとなり、全身性の代謝調節とかかわっている。
本研究はmiR-494がⅡa型筋線維の制御機構の一端を担うことを明らかにしたことから、今後、加齢や生活習慣病に対する骨格筋を標的とする創薬へ貢献できると考えている。