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

2017 Fiscal Year Final Research Report

• 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
• Keywords: 骨格筋 / 遅筋化 / 転写コファクター / 運動刺激

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.

Free Research Field

スポーツ医学