Linked Life Data

19405813

Source:http://linkedlifedata.com/resource/pubmed/id/19405813

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pubmed-article:19405813pubmed:abstractTextMyostatin is a member of the transformating growth factor-beta (TGF-beta) superfamily of proteins and is produced almost exclusively in skeletal muscle tissue, where it is secreted and circulates as a serum protein. Myostatin acts as a negative regulator of muscle mass through the canonical SMAD2/3/4 signaling pathway. Naturally occurring myostatin mutants exhibit a 'double muscling' phenotype in which muscle mass is dramatically increased as a result of both hypertrophy and hyperplasia. Myostatin is naturally inhibited by its own propeptide; therefore, we assessed the impact of adeno-associated virus-8 (AAV8) myostatin propeptide vectors when systemically introduced in MF-1 mice. We noted a significant systemic increase in muscle mass in both slow and fast muscle phenotypes, with no evidence of hyperplasia; however, the nuclei-to- cytoplasm ratio in all myofiber types was significantly reduced. An increase in muscle mass in slow (soleus) muscle led to an increase in force output; however, an increase in fast (extensor digitorum longus [EDL]) muscle mass did not increase force output. These results suggest that the use of gene therapeutic regimens of myostatin inhibition for age-related or disease-related muscle loss may have muscle-specific effects.lld:pubmed
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pubmed-article:19405813pubmed:articleTitleAdeno-associated virus-8-mediated intravenous transfer of myostatin propeptide leads to systemic functional improvements of slow but not fast muscle.lld:pubmed
pubmed-article:19405813pubmed:affiliationSWAN Institute of Biomedical and Life Sciences, School of Biological Sciences, Royal Holloway-University of London, Egham, UK.lld:pubmed
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