2023 Fiscal Year Final Research Report
Development of a screening procedure for muscle hypertrophy/atrophy related molecules by using myotube cells and comprehensive gene knockdown
| Project/Area Number |
21K19737
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 59:Sports sciences, physical education, health sciences, and related fields
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| Research Institution | Nippon Sport Science University |
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Principal Investigator |
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| Project Period (FY) |
2021-07-09 – 2024-03-31
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| Keywords | siRNA / 骨格筋 / NSMAF |
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| Outline of Final Research Achievements |
Systemic hyperinflammation during ageing induces skeletal muscle atrophy via an increase in blood inflammatory cytokines (e.g. TNFα). We performed comprehensive knockdown (KD) using small interfering RNA (RNAi) on phospholipid metabolic enzymes involved in inflammation and discovered Nsmaf (neutral sphingomyelinase activation associated factor), which has a strong effect on skeletal muscle morphology. Nsmaf KD increased skeletal muscle protein synthesis but decreased muscle fibre diameter, while Nsmaf overexpression had no effect. We conclude that comprehensive siRNA is effective in the search for skeletal muscle morphogenetic regulators. We also concluded that Nsmaf is a novel regulator of skeletal muscle morphology.
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| Free Research Field |
筋生理・生化学
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| Academic Significance and Societal Importance of the Research Achievements |
加齢に伴う骨格筋萎縮（サルコペニア）は日常生活動作に支障をきたす。身体動作のみならず骨格筋は代謝や内分泌にも影響を与えるため、骨格筋萎縮は加齢や慢性疾患に伴う代謝異常の促進にも関与する。したがって加齢時や慢性時の骨格筋萎縮を予防することが重要である。慢性的な炎症がこれら骨格筋萎縮に影響を与えることが知られており、今後炎症反応に影響を与える様々なタンパク質を網羅的にノックダウンすることで慢性炎症による骨格筋萎縮に影響を与えるタンパク質の抽出が可能になることが期待できることを示した初めての研究成果である。この方法論は慢性炎症時の骨格筋萎縮のみならず多くの疾患に対して有効なアプローチになる。
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