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Evaluation of follistatin as a therapeutic in models of skeletal muscle atrophy associated with denervation and tenotomy

Sepulveda, Patricio V., Lamon, Severine, Hagg, Adam, Thomson, Rachel E., Winbanks, Catherine E., Qian, Hongwei, Bruce, Clinton R., Russell, Aaron P. and Gregorevic, Paul 2015, Evaluation of follistatin as a therapeutic in models of skeletal muscle atrophy associated with denervation and tenotomy, Scientific reports, vol. 5, Article Number : 17535, pp. 1-11, doi: 10.1038/srep17535.

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Title Evaluation of follistatin as a therapeutic in models of skeletal muscle atrophy associated with denervation and tenotomy
Author(s) Sepulveda, Patricio V.
Lamon, SeverineORCID iD for Lamon, Severine orcid.org/0000-0002-3271-6551
Hagg, Adam
Thomson, Rachel E.
Winbanks, Catherine E.
Qian, Hongwei
Bruce, Clinton R.ORCID iD for Bruce, Clinton R. orcid.org/0000-0002-0515-3343
Russell, Aaron P.ORCID iD for Russell, Aaron P. orcid.org/0000-0002-7323-9501
Gregorevic, Paul
Journal name Scientific reports
Volume number 5
Season Article Number : 17535
Start page 1
End page 11
Total pages 11
Publisher Nature Publishing Group
Place of publication London, Eng.
Publication date 2015
ISSN 2045-2322
Summary Follistatin is an inhibitor of TGF-β superfamily ligands that repress skeletal muscle growth and promote muscle wasting. Accordingly, follistatin has emerged as a potential therapeutic to ameliorate the deleterious effects of muscle atrophy. However, it remains unclear whether the anabolic effects of follistatin are conserved across different modes of non-degenerative muscle wasting. In this study, the delivery of a recombinant adeno-associated viral vector expressing follistatin (rAAV:Fst) to the hind-limb musculature of mice two weeks prior to denervation or tenotomy promoted muscle hypertrophy that was sufficient to preserve muscle mass comparable to that of untreated sham-operated muscles. However, administration of rAAV:Fst to muscles at the time of denervation or tenotomy did not prevent subsequent muscle wasting. Administration of rAAV:Fst to innervated or denervated muscles increased protein synthesis, but markedly reduced protein degradation only in innervated muscles. Phosphorylation of the signalling proteins mTOR and S6RP, which are associated with protein synthesis, was increased in innervated muscles administered rAAV:Fst, but not in treated denervated muscles. These results demonstrate that the anabolic effects of follistatin are influenced by the interaction between muscle fibres and motor nerves. These findings have important implications for understanding the potential efficacy of follistatin-based therapies for non-degenerative muscle wasting.
Language eng
DOI 10.1038/srep17535
Field of Research 111699 Medical Physiology not elsewhere classified
Socio Economic Objective 920116 Skeletal System and Disorders (incl. Arthritis)
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2015, Nature Publishing Group
Persistent URL http://hdl.handle.net/10536/DRO/DU:30080279

Document type: Journal Article
Collection: School of Exercise and Nutrition Sciences
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Created: Wed, 16 Dec 2015, 06:02:24 EST

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