the basic analysis of molecular mecahnisms of novel fast-to-slow fiber type swiching involeved in transcriptional cofactor Vgll2.

• Project/Area Number: 15K16501
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Sports science
• Research Institution: National Cardiovascular Center Research Institute
• Principal Investigator: Honda Masahiko 国立研究開発法人国立循環器病研究センター, 研究所, 研究員 (10455545)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 骨格筋 / 遅筋化 / 転写コファクター / 運動刺激 / 運動 / 代償性負荷 / 筋線維タイプ

Outline of Final Research Achievements

In this study, we demonstrated that transcriptional cofactor Vgll2 plays essential role in skeletal muscle remodeling induced by chronic functional overload (OVL). We observed wild type plantaris muscles exhibit slower muscle phenotype after 6-week OVL, while fiber type composition in Vgll2 knock-out (KO) plantaris was not affected. Moreover, Vgll2 protein is increased by OVL and decreased by denervation, suggesting Vgll2 protein levels correlated with muscle usage. We also found calcineurin signaling activates TEAD-dependent transcriptional activity via the nuclear transportation of Vgll2 in myogenic cell line C2C12. Unexpectedly, we found Vgll2 interacts with NFATc1 in OVL plantaris muscles in addition to well-known partner transcription factors like TEAD1 and MEF2c. Taken together, our results suggest Vgll2 is more multi-functional than previously thought. Therefore, molecular mechanisms involved in Vgll2 can be novel therapeutic target to improve skeletal muscle function.

Research Products

• [Journal Article] Vestigial-like 2 contributes to normal muscle fiber type distribution in mice (2017)
  • Author(s): Honda Masahiko、Hidaka Kyoko、Fukada So-ichiro、Sugawa Ryo、Shirai Manabu、Ikawa Masahito、Morisaki Takayuki
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 734-740
  • DOI: 10.1038/s41598-017-07149-0
  • NAID: 120006957431
  • Peer Reviewed / Open Access
• [Presentation] 慢性的な機械的過負荷に対する骨格筋の適応におけるVgll2の機能解析 (2017)
  • Author(s): 本多賢彦、日高京子、土持裕胤、森崎隆幸
  • Organizer: 2017年度生命科学系学会合同年次大会
• [Presentation] Functional analysis of Vgll2 in chronic overload-induced skeletal muscle remodeling (2016)
  • Author(s): Masahiko Honda, Kyoko Hidaka, Hirotsugu Tsuchimochi, Takayuki Morisaki
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: 神奈川県横浜市
  • Year and Date: 2016-11-30
• [Presentation] Functional analysis of Vgll2 in muscle plasticity (2016)
  • Author(s): Masahiko Honda
  • Organizer: 第四回骨格筋若手の会
  • Place of Presentation: 愛知県名古屋市
  • Year and Date: 2016-11-14
• [Presentation] マウスの遅筋表現型制御におけるVgll2の機能解析 (2016)
  • Author(s): 本多賢彦、日高京子、深田宗一朗、森崎隆幸
  • Organizer: 第二回日本筋学会学術集会
  • Place of Presentation: 東京都小平市
  • Year and Date: 2016-08-05
• [Presentation] Impact of Vgll2 deficiency on fetal myogenesis (2015)
  • Author(s): Honda, M., Hidaka, K., Sugawa, R., Fukada, S., Sumie, N., and Morisaki, T.
  • Organizer: 第38回分子生物学会年会
  • Place of Presentation: 兵庫県神戸市
  • Year and Date: 2015-12-01