IGF-1 regulates PEAR1 through Egr1 to promote skeletal muscle post-injury regeneration

Insulin-like growth factor 1 (IGF-1) is a key regulator of skeletal muscle growth and regeneration. In this study, we demonstrate that IGF-1 promotes C2C12 myoblast proliferation in a dose- and time-dependent manner. Mechanistically, IGF-1 induces the expression of early growth response 1 (Egr1), a transcription factor that directly binds to the promoter region of platelet endothelial aggregation receptor 1 (PEAR1) and enhances its transcription. Upregulation of PEAR1 subsequently facilitates myoblast proliferation by activating the Notch signaling pathway. Furthermore, IGF-1-induced activation of the Egr1-PEAR1 cascade enhances muscle stem cell (MuSC) proliferation and accelerates skeletal muscle regeneration following injury in vivo. Collectively, this study reveals the critical role of the IGF-1-Egr1-PEAR1 regulatory axis in skeletal muscle regeneration, providing novel mechanistic insight into IGF-1-mediated muscle repair.