PGC-1α modulates necrosis, inflammatory response, and fibrotic tissue formation in injured skeletal muscle. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Dinulovic, Ivana; Furrer, Regula; Di Fulvio, Sabrina; Ferry, Arnaud; Beer, Markus; Handschin, Christoph
• Is Part Of: Skeletal muscle. Volume 6:Issue 1(2016)
• Page Start: 1
• Page End: 11
• Publication Date: 2016-12
• Subjects: PGC-1α -- Regeneration -- Inflammation -- Fibrosis -- Macrophages -- Necrosis; Musculoskeletal system -- Periodicals; 612.7
• DOI: 10.1186/s13395-016-0110-x
• Languages: English
• ISSNs: 2044-5040

Abstract

Abstract 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. 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.