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Evaluation of follistatin as a therapeutic in models of skeletal muscle atrophy associated with denervation and tenotomy
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 o...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4675991/ https://www.ncbi.nlm.nih.gov/pubmed/26657343 http://dx.doi.org/10.1038/srep17535 |
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author | Sepulveda, Patricio V. Lamon, Séverine Hagg, Adam Thomson, Rachel E. Winbanks, Catherine E. Qian, Hongwei Bruce, Clinton R. Russell, Aaron P. Gregorevic, Paul |
author_facet | Sepulveda, Patricio V. Lamon, Séverine Hagg, Adam Thomson, Rachel E. Winbanks, Catherine E. Qian, Hongwei Bruce, Clinton R. Russell, Aaron P. Gregorevic, Paul |
author_sort | Sepulveda, Patricio V. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4675991 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-46759912015-12-16 Evaluation of follistatin as a therapeutic in models of skeletal muscle atrophy associated with denervation and tenotomy Sepulveda, Patricio V. Lamon, Séverine Hagg, Adam Thomson, Rachel E. Winbanks, Catherine E. Qian, Hongwei Bruce, Clinton R. Russell, Aaron P. Gregorevic, Paul Sci Rep Article 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. Nature Publishing Group 2015-12-11 /pmc/articles/PMC4675991/ /pubmed/26657343 http://dx.doi.org/10.1038/srep17535 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Sepulveda, Patricio V. Lamon, Séverine Hagg, Adam Thomson, Rachel E. Winbanks, Catherine E. Qian, Hongwei Bruce, Clinton R. Russell, Aaron P. Gregorevic, Paul Evaluation of follistatin as a therapeutic in models of skeletal muscle atrophy associated with denervation and tenotomy |
title | Evaluation of follistatin as a therapeutic in models of skeletal muscle atrophy associated with denervation and tenotomy |
title_full | Evaluation of follistatin as a therapeutic in models of skeletal muscle atrophy associated with denervation and tenotomy |
title_fullStr | Evaluation of follistatin as a therapeutic in models of skeletal muscle atrophy associated with denervation and tenotomy |
title_full_unstemmed | Evaluation of follistatin as a therapeutic in models of skeletal muscle atrophy associated with denervation and tenotomy |
title_short | Evaluation of follistatin as a therapeutic in models of skeletal muscle atrophy associated with denervation and tenotomy |
title_sort | evaluation of follistatin as a therapeutic in models of skeletal muscle atrophy associated with denervation and tenotomy |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4675991/ https://www.ncbi.nlm.nih.gov/pubmed/26657343 http://dx.doi.org/10.1038/srep17535 |
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