Myostatin Orchestrates miR-124-Mediated Epigenetic Silencing of ITGB1 to Suppress Skeletal Muscle Growth

Although myostatin is a well-established inhibitor of myogenesis, its downstream mediators remain poorly characterized. This study identified integrin β1 (ITGB1), an integrin family member, as a novel mediator in myostatin signaling. Our results demonstrated that ITGB1 promoted C2C12 myoblast differentiation. Myostatin treatment significantly downregulated ITGB1 expression and suppressed myogenic differentiation, whereas ITGB1 overexpression reversed the inhibitory effects of myostatin. Bioinformatic prediction and dual-luciferase reporter assay revealed that miR-124 suppressed ITGB1 expression by targeting its 3′ untranslated region (UTR). Importantly, miR-124 reduced C2C12 myoblast differentiation by suppressing ITGB1. Furthermore, myostatin treatment markedly enhanced the expression of miR-124 in C2C12 myoblasts, thereby suppressing ITGB1. In vivo, blocking the myostatin/miR-124/ITGB1 pathway significantly promoted skeletal muscle growth in mice. Accordingly, these data revealed that myostatin negatively regulated skeletal muscle growth in mice by promoting the miR-124-mediated epigenetic repression of ITGB1. Our findings provide new insights into the regulation of myogenesis via myostatin signaling.