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dc.contributor.authorSepulveda, PV
dc.contributor.authorLamon, S
dc.contributor.authorHagg, A
dc.contributor.authorThomson, RE
dc.contributor.authorWinbanks, CE
dc.contributor.authorQian, H
dc.contributor.authorBruce, CR
dc.contributor.authorRussell, AP
dc.contributor.authorGregorevic, P
dc.date.accessioned2021-02-05T00:21:48Z
dc.date.available2021-02-05T00:21:48Z
dc.date.issued2015-12-11
dc.identifierpii: srep17535
dc.identifier.citationSepulveda, P. V., Lamon, S., Hagg, A., Thomson, R. E., Winbanks, C. E., Qian, H., Bruce, C. R., Russell, A. P. & Gregorevic, P. (2015). Evaluation of follistatin as a therapeutic in models of skeletal muscle atrophy associated with denervation and tenotomy. SCIENTIFIC REPORTS, 5 (1), https://doi.org/10.1038/srep17535.
dc.identifier.issn2045-2322
dc.identifier.urihttp://hdl.handle.net/11343/259974
dc.description.abstractFollistatin 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.
dc.languageEnglish
dc.publisherNATURE PUBLISHING GROUP
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleEvaluation of follistatin as a therapeutic in models of skeletal muscle atrophy associated with denervation and tenotomy
dc.typeJournal Article
dc.identifier.doi10.1038/srep17535
melbourne.affiliation.departmentAnatomy and Neuroscience
melbourne.affiliation.facultyMedicine, Dentistry & Health Sciences
melbourne.source.titleScientific Reports
melbourne.source.volume5
melbourne.source.issue1
dc.rights.licenseCC BY
melbourne.elementsid1076548
melbourne.contributor.authorGregorevic, Paul
melbourne.contributor.authorThomson, Rachel
melbourne.contributor.authorQian, Hongwei
melbourne.contributor.authorHagg, Adam
dc.identifier.eissn2045-2322
melbourne.accessrightsOpen Access


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