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



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.



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.



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.
Biozentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland.
Ivana
I
Dinulovic
Biozentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland.
Regula
R
Furrer
Biozentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland.
Sabrina
S
Di Fulvio
Thérapie des maladies du muscle strié INSERM U974 - CNRS UMR7215 - UPMC UM76, Institut de Myologie and University Rene Descartes, 47, bld de l'Hôpital, G.H. Pitié-Salpétrière, 75013 Paris, France.
Arnaud
A
Ferry
Biozentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland.
Markus
M
Beer
Biozentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland.
Christoph
0000-0003-0603-1097
C
Handschin
D000818:Animals; D004179:Cobra Cardiotoxin Proteins; D005355:Fibrosis / Q000378:metabolism / Q000503:physiopathology; D015870:Gene Expression; D006909:Hydroxyproline / Q000378:metabolism; D008264:Macrophages / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000293:injuries / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D009220:Myositis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D009336:Necrosis; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000235:genetics / Q000502:physiology*; D012038:Regeneration
D004179:Cobra Cardiotoxin Proteins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D006909:Hydroxyproline
Fibrosis; Inflammation; Macrophages; Necrosis; PGC-1α; Regeneration