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

PGC-1α 调节受损骨骼肌的坏死、炎症反应和纤维化组织形成

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作者:Ivana Dinulovic, Regula Furrer, Sabrina Di Fulvio, Arnaud Ferry, Markus Beer, Christoph Handschin

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 γ coactivator 1α (PGC-1α) exerts therapeutic effects in several muscle pathologies, but its role in damage-induced muscle regeneration is unclear.

Conclusions

PGC-1α exerts beneficial effects on muscle inflammation that might contribute to the therapeutic effects of elevated muscle PGC-1α in different models of muscle wasting.

Methods

Using muscle-specific gain- and loss-of-function models for PGC-1α 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-1α-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-1α exerts beneficial effects on muscle inflammation that might contribute to the therapeutic effects of elevated muscle PGC-1α in different models of muscle wasting.

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