Study of muscle hypertrophy regulated by the lipid sphingomyelin synthesis system and development of methods to promote muscle hypertrophy

• Project/Area Number: 18K11089
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Okayama University of Science
• Principal Investigator: Nagata Yosuke 岡山理科大学, 理学部, 講師 (50401211)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 骨格筋 / 筋肥大 / スフィンゴミエリン / スフィンゴミエリン合成酵素 / 細胞融合 / C2C12 / 筋分化

Outline of Final Research Achievements

We found that forced expression of sphingomyelin synthases Sms1 and Sms2 in the mouse myoblast cell line C2C12 resulted in the formation of large myotubes with a high number of myonuclei, and that siRNA-based knockdown suppressed myotube formation. MyoD, Myf5, myogenin, and MRF4 were not significantly altered by forced expression of Sms1. On the other hand, an increase in myocyte fusion-related protein myomaker positive signal was detected, indicating that the increase in sphingomyelin induced by forced expression of sphingomyelin shynthetases promotes myocyte fusion and the formation of giant myotubes rather than muscle differentiation.

Academic Significance and Societal Importance of the Research Achievements

骨格筋はわれわれが体を動かすために必要な組織であり，加齢に伴う運動機能の低下を防ぐためには骨格筋の再生能と可塑性のメカニズムを解明し，筋量を維持する方法を開発することが有効と考えられる。骨格筋の機能を担う筋線維は多数の筋前駆細胞の融合によって形成され，筋肥大の際には既存の筋線維に新たな筋前駆細胞が融合する。本研究では，骨格筋の細胞融合に膜脂質の一種であるスフィンゴミエリンが関与することを明らかにし，筋肥大の促進に役立てられる可能性を示すことができた。

Research Products

• [Journal Article] スフィンゴ脂質による骨格筋形成のコントロール (2020)
  • Author(s): 長田洋輔，松田良一
  • Journal Title: 細胞 Volume: 52 Pages: 43-46
• [Journal Article] Cell surface flip-flop of phosphatidylserine is critical for PIEZO1-mediated myotube formation (2018)
  • Author(s): Tsuchiya Masaki、Hara Yuji、Okuda Masaki、Itoh Karin、Nishioka Ryotaro、Shiomi Akifumi、Nagao Kohjiro、Mori Masayuki、Mori Yasuo、Ikenouchi Junichi、Suzuki Ryo、Tanaka Motomu、Ohwada Tomohiko、Aoki Junken、Kanagawa Motoi、Toda Tatsushi、Nagata Yosuke、Matsuda Ryoichi、Takayama Yasunori、Tominaga Makoto、Umeda Masato
  • Journal Title: Nature Communications Volume: 9 Issue: 1 Pages: 2049-2049
  • DOI: 10.1038/s41467-018-04436-w
  • NAID: 120006471161
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] スフィンゴミエリン合成酵素による骨格筋形成の制御についての研究 (2019)
  • Author(s): 長田洋輔，松田良一
  • Organizer: 日本脂質生化学会
• [Presentation] スフィンゴミエリン合成酵素による筋芽細胞の機能制御 (2018)
  • Author(s): 長田 洋輔，松田 良一
  • Organizer: 動物学会第89回札幌大会