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

JL Chen; KL Walton; A Hagg; TD Colgan; K Johnson; H Qian; P Gregorevic; CA Harrison

Journal article

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

JL Chen, KL Walton, A Hagg, TD Colgan, K Johnson, H Qian, P Gregorevic, CA Harrison

Proceedings of the National Academy of Sciences of the United States of America | Published : 2017

DOI: 10.1073/pnas.1620013114

Abstract

The transforming growth factor-β (TGF-β) network of ligands and intracellular signaling proteins is a subject of intense interest within the field of skeletal muscle biology. To define the relative contribution of endogenous TGF-β proteins to the negative regulation of muscle mass via their activation of the Smad2/3 signaling axis, we used local injection of adeno-associated viral vectors (AAVs) encoding ligand-specific antagonists into the tibialis anterior (TA) muscles of C57BL/6 mice. Eight weeks after AAV injection, inhibition of activin A and activin B signaling produced moderate (-20%), but significant, increases in TA mass, indicating that endogenous activins repress muscle growth. In..

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University of Melbourne Researchers

Hongwei Qian Author

Paul Gregorevic Author

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Grants

Awarded by National Health and Medical Research Council (NHMRC) Australia

Awarded by National Health and Medical Research Council of Australia

Funding Acknowledgements

We acknowledge the technical assistance of the Monash Health Translation Precinct Medical Genomics Facility-Australian Cancer Research Foundation Centre for Cancer Genomic Medicine. C.A.H. and P.G. were supported by grant and fellowship funding (Grants 1078907, 1046782, and 1077703) from the National Health and Medical Research Council (NHMRC) Australia. J.L.C. was supported by fellowships from the Cancer Council Victoria and the Endocrine Society Australia. An Early Career Seed Grant from the Victorian Cancer Agency supported K.L.W. The Hudson Institute of Medical Research and Baker Heart and Diabetes Institute are supported in part by the Operational Infrastructure Support Program of the Victorian Government.