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Evaluation of follistatin as a therapeutic in models of skeletal muscle atrophy associated with denervation and tenotomy.
- Source :
-
Scientific reports [Sci Rep] 2015 Dec 11; Vol. 5, pp. 17535. Date of Electronic Publication: 2015 Dec 11. - Publication Year :
- 2015
-
Abstract
- 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.
- Subjects :
- Animals
Dependovirus genetics
Disease Models, Animal
Follistatin metabolism
Gene Expression
Gene Transfer Techniques
Genetic Vectors administration & dosage
Genetic Vectors genetics
Hypertrophy
Mice
Muscle, Skeletal innervation
Muscle, Skeletal metabolism
Muscle, Skeletal pathology
Muscular Atrophy therapy
Signal Transduction
TOR Serine-Threonine Kinases metabolism
Transduction, Genetic
Denervation adverse effects
Follistatin genetics
Genetic Therapy
Muscular Atrophy etiology
Muscular Atrophy pathology
Tenotomy adverse effects
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 5
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 26657343
- Full Text :
- https://doi.org/10.1038/srep17535