PGC-1alpha modulates necrosis, inflammatory response, and fibrotic tissue formation in injured skeletal muscle

BACKGROUND: Skeletal muscle tissue has an enormous regenerative capacity that is instrumental for a successful defense against muscle injury and wasting. The peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha) exerts therapeutic effects in several muscle pathologies, but its role in damage-induced muscle regeneration is unclear.
METHODS: Using muscle-specific gain- and loss-of-function models for PGC-1alpha in combination with the myotoxic agent cardiotoxin (CTX), we explored the role of this transcriptional coactivator in muscle damage and inflammation.
RESULTS: Interestingly, we observed PGC-1alpha-dependent effects at the early stages of regeneration, in particular regarding macrophage accumulation and polarization from the pro-inflammatory M1 to the anti-inflammatory M2 type, a faster resolution of necrosis and protection against the development of fibrosis after multiple CTX-induced injuries.
CONCLUSIONS: PGC-1alpha exerts beneficial effects on muscle inflammation that might contribute to the therapeutic effects of elevated muscle PGC-1alpha in different models of muscle wasting.