Folic acid (FA) plays multiple roles in many biological processes. Myoblast intakes FA through endocytosis by folate receptor 1 (Folr1), which has vital role in regulating muscle development. However, the mechanism remains unclear. In this study, FA supplement experiment showed that FA promoted C2C12 cell differentiation through Folr1. Further exploration found that FA could promote C2C12 cell migration through Folr1 interacting with RhoA. Then stimulated RhoA/ROCK/LIMK/cofilin signaling pathway, and affected the distribution of microfilaments to improve C2C12 cell migration. Meanwhile, mice experiments also proved that FA could activate the expression of RhoA/ROCK/LIMK/cofilin signaling pathway in vivo and accelerate the process of skeletal muscle regeneration in mice. This discovery is helpful to further understand the molecular mechanism of FA regulating muscle development and provide new ideas for the treatment of muscle diseases. All rights reserved, Elsevier.

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