The TGF-β Signalling Network in Muscle Development, Adaptation and Disease

  • Justin L. Chen
  • Timothy D. Colgan
  • Kelly L. Walton
  • Paul GregorevicEmail author
  • Craig A. HarrisonEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 900)


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.


Skeletal muscle wasting Neuromuscular disorders Myostatin Activin TGF-β network 



This work was supported by grant funding (526648, 566820, 1006488, 1078907) from the National Health and Medical Research Council (NHMRC, Australia). JLC is supported by a postdoctoral fellowship from the Cancer Council Victoria. KLW is supported by an Early Career Seed from the Victorian Cancer Agency. PG is supported by a Career Development Fellowship (1046782) from the NHMRC. JLC and TDC were previously supported by Australian Postgraduate Awards. PG was previously supported by a Senior Research Fellowship, sponsored by Pfizer Australia. CAH was supported by a Career Development Fellowship (1013533) from the NHMRC. Hudson Institute of Medical Research and Baker IDI Heart and Diabetes Institute are supported in part by the Operational Infrastructure Support Program of the Victorian Government.

Conflict of Interest

The authors declare no conflict of interest.


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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Justin L. Chen
    • 1
    • 2
    • 3
    • 4
  • Timothy D. Colgan
    • 3
    • 5
  • Kelly L. Walton
    • 1
    • 2
  • Paul Gregorevic
    • 3
    • 4
    • 5
    • 6
    Email author
  • Craig A. Harrison
    • 1
    • 2
    • 7
    Email author
  1. 1.Centre for Endocrinology and MetabolismHudson Institute of Medical ResearchClaytonAustralia
  2. 2.Department of Molecular and Translational SciencesMonash UniversityMelbourneAustralia
  3. 3.Muscle Research and Therapeutics DevelopmentBaker IDI Heart and Diabetes InstituteMelbourneAustralia
  4. 4.Department of Biochemistry and Molecular BiologyMonash UniversityMelbourneAustralia
  5. 5.Department of PhysiologyThe University of MelbourneMelbourneAustralia
  6. 6.Department of Neurology, School of MedicineThe University of WashingtonSeattleUSA
  7. 7.Department of PhysiologyMonash UniversityMelbourneAustralia

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