Abstract
BackgroundSkeletal 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.MethodsUsing 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.ResultsInterestingly, 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.ConclusionsPGC-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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13395-016-0110-x) contains supplementary material, which is available to authorized users.
Highlights
Skeletal muscle tissue has an enormous regenerative capacity that is instrumental for a successful defense against muscle injury and wasting
There is a significant difference between WT and Musclespecific Peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) transgenic mice (mTG) regarding the proportion of F4/80+CD80+CD163- M1 macrophages, this difference is very small (1.3 % in WT vs 0.2 % in mTG) and the amount of M1 macrophages seems neglectable in healthy muscles
In summary, we provide evidence that muscles with higher levels of PGC-1α are preconditioned for faster resolution of inflammation and necrosis as well as a prevention of fibrosis after repeated injury
Summary
Skeletal muscle tissue has an enormous regenerative capacity that is instrumental for a successful defense against muscle injury and wasting. Damaged muscle fibers undergo necrosis, and as a consequence, muscle-resident mast cells and macrophages are first activated to eradicate cell debris and make room for newly formed muscle fibers [2]. By secreting cytokines such as tumor necrosis factor α (TNFα) and interleukin 6 (IL-6), these cells subsequently attract neutrophils, which invade the damaged area within hours [2]. Timely attraction of macrophages, the switch between subclasses, and the precise termination of the activity of these cells at the end of the regenerative process are prerequisites for the successful activation, proliferation, and differentiation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
