title: The TGF-β Signalling Network in Muscle Development, Adaptation and Disease.
abstract: Skeletal muscle possesses remarkable ability to change its size and force-producing 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 identified 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.
authors.affiliation: Centre for Endocrinology and Metabolism, Hudson Institute of Medical Research, Clayton, VIC, 3168, Australia.|Department of Molecular and Translational Sciences, Monash University, Melbourne, VIC, Australia.|Muscle Research and Therapeutics Development, Baker IDI Heart and Diabetes Institute, Melbourne, VIC, 3004, Australia.|Department of Biochemistry and Molecular Biology, Monash University, Melbourne, VIC, Australia.
authors.forename: Justin L
authors.initials: JL
authors.lastname: Chen
authors.affiliation: Muscle Research and Therapeutics Development, Baker IDI Heart and Diabetes Institute, Melbourne, VIC, 3004, Australia.|Department of Physiology, The University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Colgan
authors.affiliation: Centre for Endocrinology and Metabolism, Hudson Institute of Medical Research, Clayton, VIC, 3168, Australia.|Department of Molecular and Translational Sciences, Monash University, Melbourne, VIC, Australia.
authors.forename: Kelly L
authors.initials: KL
authors.lastname: Walton
authors.affiliation: Muscle Research and Therapeutics Development, Baker IDI Heart and Diabetes Institute, Melbourne, VIC, 3004, Australia. Paul.Gregorevic@bakeridi.edu.au.|Department of Biochemistry and Molecular Biology, Monash University, Melbourne, VIC, Australia. Paul.Gregorevic@bakeridi.edu.au.|Department of Physiology, The University of Melbourne, Melbourne, VIC, Australia. Paul.Gregorevic@bakeridi.edu.au.|Department of Neurology, School of Medicine, The University of Washington, Seattle, WA, USA. Paul.Gregorevic@bakeridi.edu.au.
authors.forename: Paul
authors.initials: P
authors.lastname: Gregorevic
authors.affiliation: Centre for Endocrinology and Metabolism, Hudson Institute of Medical Research, Clayton, VIC, 3168, Australia. Craig.Harrison@hudson.org.au.|Department of Molecular and Translational Sciences, Monash University, Melbourne, VIC, Australia. Craig.Harrison@hudson.org.au.|Department of Physiology, Monash University, Melbourne, VIC, Australia. Craig.Harrison@hudson.org.au.
authors.forename: Craig A
authors.initials: CA
authors.lastname: Harrison
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D002100:Cachexia / Q000209:etiology; D006706:Homeostasis; D006801:Humans; D008382:Marfan Syndrome / Q000209:etiology; D024510:Muscle Development; D009136:Muscular Dystrophies / Q000209:etiology; D012038:Regeneration; D055948:Sarcopenia / Q000209:etiology; D015398:Signal Transduction / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000502:physiology*
chemical_list: D016212:Transforming Growth Factor beta
keywords: Activin; Myostatin; Neuromuscular disorders; Skeletal muscle wasting; TGF-β network