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Cited by 116Muscle Physiology and DisordersTGF-β signaling in diseasesNeurogenetic and Muscular Disorders Research

Specific targeting of TGF-β family ligands demonstrates distinct roles in the regulation of muscle mass in health and disease

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Chen, Justin L., Walton, Kelly L., Hagg, Adam, Colgan, Timothy D., Johnson, Katharine, Qian, Hongwei, Gregorevic, Paul, Harrison, Craig A.·2017·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.1620013114PMC PMC5495232
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Abstract

Significance: Myostatin, via activation of the Smad2/3 pathway, has long been recognized as the body’s major negative regulator of skeletal muscle mass. In this study, however, we demonstrate that other TGF-β proteins, particularly activin A and activin B, act in concert with myostatin to repress muscle growth. Preventing activin and myostatin signaling in the tibialis anterior muscles of mice resulted in massive hypertrophy (>150%), which was dependent upon both the complete inhibition of the Smad2/3 pathway and activation of the parallel bone morphogenetic protein (BMP)/Smad1/5 axis. Using this approach in models of muscular dystrophy and cancer cachexia increased muscle mass or prevented muscle wasting, respectively, highlighting the potential therapeutic advantages of complete inhibition of Smad2/3 ligand activity in skeletal muscle.

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Cited by

Sorted by citations

Authors
Chen, J. L., Walton, K. L., Hagg, A., Colgan, T. D., Johnson, K., Qian, H., Gregorevic, P., & Harrison, C. A.
Affiliations
  • Baker Heart and Diabetes Institute (AU)
  • Hudson Institute of Medical Research (AU)
  • Monash University (AU)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2017-06-12
Volume
114
Issue
26
Pages
E5266-E5275
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.1620013114
PMC
PMC5495232
OpenAlex
W2627003412
Cited by
116
References
7
Citations by year
2026: 8 · 2025: 9 · 2024: 7 · 2023: 12 · 2022: 21 · 2021: 14 · 2020: 15 · 2019: 14 · 2018: 14 · 2017: 2
FWCI
5.03
Type
journal article
Language
en
Open access
Licence
www.pnas.org/site/misc/userlicense.xhtml (vor, 183 d)
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Swinburne figshare (Swinburne University of Technology) (submittedVersion)
Funders
Department of Health, Australian Government | National Health and Medical Research Council (NHMRC) (1078907)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
  • Health Sciences › Medicine › Genetics › Neurogenetic and Muscular Disorders Research
Keywords
skeletal muscle mass, muscle hypertrophy, activin A, activin B, myostatin, Smad2/3 signaling, adeno-associated virus vectors, protein synthesis, ubiquitin-dependent protein degradation, muscular dystrophy, cancer cachexia, muscle atrophy
MeSH terms
Dependovirus, Animals, Genetic Vectors, Male, Muscle Proteins, Muscular Diseases, Organ Size, Signal Transduction, Transforming Growth Factor beta, Gene Targeting, Muscle, Skeletal, Activins, Mice, Smad Proteins

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