The TGF-β signalling network in muscle development, adaptation and disease

Skeletal muscle possesses remarkable ability to change its size and forceproducing capacity in response to physiological stimuli. Impairment of the cellular processes that govern these attributes also affects muscle mass and function in pathological conditions. Myostatin, a member of the TGF-β family, has been identifi ed as a key regulator of muscle development, and adaptation in adulthood. In muscle, myostatin binds to its type I (ALK4/5) and type II (ActRIIA/B) receptors to initiate Smad2/3 signalling and the regulation of target genes that co-ordinate the balance between protein synthesis and degradation. Interestingly, evidence is emerging that other TGF-β proteins act in concert with myostatin to regulate the growth and remodelling of skeletal muscle. Consequently, dysregulation of TGF-β proteins and their associated signalling components is increasingly being implicated in muscle wasting associated with chronic illness, ageing, and inactivity. The growing understanding of TGF-β biology in muscle, and its potential to advance the development of therapeutics for muscle-related conditions is reviewed here.