Abstract:
Tumor necrosis factor α (TNFα) exhibits diverse biological functions; however, its regulatory roles in myogenesis are not fully understood. In the present study, we explored the function of
TNFα in myoblast proliferation, differentiation, migration, and myotube fusion in primary myoblasts and C2C12 cells. To this end, we constructed
TNFα muscle-conditional knockout (
TNFα-CKO) mice and compared them with
flox mice to assess the effects of
TNFα knockout on skeletal muscles. Results indicated that
TNFα-CKO mice displayed phenotypes such as accelerated muscle development, enhanced regenerative capacity, and improved exercise endurance compared to
flox mice, with no significant differences observed in major visceral organs or skeletal structure. Using label-free proteomic analysis, we found that
TNFα-CKO altered the distribution of several muscle development-related proteins, such as Hira, Casz1, Casp7, Arhgap10, Gas1, Diaph1, Map3k20, Cfl2, and Igf2, in the nucleus and cytoplasm. Gene set enrichment analysis (GSEA) further revealed that
TNFα deficiency resulted in positive enrichment in oxidative phosphorylation and MyoD targets and negative enrichment in JAK-STAT signaling. These findings suggest that
TNFα-CKO positively regulates muscle growth and development, possibly via these newly identified targets and pathways.