Pharmacological activation of Rev-erbα partially alleviates LPS-induced inflammation in C2C12 myoblasts through the NF-κB pathway to influence myogenic differentiation

Rev-erbα is a key nuclear receptor and transcriptional repressor that controls circadian rhythm, metabolism and inflammation, but its role in skeletal muscle inflammatory injury remains unclear. This study investigated Rev-erbα’s regulatory effects on LPS-induced inflammation in C2C12 myoblasts. C2C12 myoblasts were used to analyze Rev-erbα expression during myogenic differentiation. Inflammation was induced with LPS (1 μg/mL) to evaluate the expression of relevant indices expression using RT-PCR, Western blotting, and RNA-seq. Rev-erbα was knocked down by siRev-erbα or activated by SR9009 (10 μM), and the expression of relevant genes was examined under LPS-treated conditions. Flow cytometry was used to evaluate the effect of SR9009 on the cell cycle distribution. Rev-erbα was upregulated during myogenic differentiation. LPS downregulated MyoD, myogenin, Tcap and activated the NF-κB pathway. While LPS triggered a rapid but transient REV-ERBα protein response. Rev-erbα knockdown exacerbated inflammation. SR9009 reduced the p-NF-κB p65/NF-κB p65 ratio, inflammatory cytokines and atrophy-related gene expression. SR9009 promoted cell cycle progression but failed to fully reverse LPS-treated downregulation of MyoD and myogenin. Rev-erbα plays a protective role against LPS-induced inflammatory injury in myoblasts. Pharmacological activation of Rev-erbα partially counteracts inflammation by inhibiting the NF-κB pathway to ensure myoblast proliferation and repair. However, myogenic differentiation was not restored.