Deacetylase inhibitors increase muscle cell size by promoting myoblast recruitment and fusion through induction of follistatin.
Dev Cell
; 6(5): 673-84, 2004 May.
Article
em En
| MEDLINE
| ID: mdl-15130492
ABSTRACT
Fusion of undifferentiated myoblasts into multinucleated myotubes is a prerequisite for developmental myogenesis and postnatal muscle growth. We report that deacetylase inhibitors favor the recruitment and fusion of myoblasts into preformed myotubes. Muscle-restricted expression of follistatin is induced by deacetylase inhibitors and mediates myoblast recruitment and fusion into myotubes through a pathway distinct from those utilized by either IGF-1 or IL-4. Blockade of follistatin expression by RNAi-mediated knockdown, functional inactivation with either neutralizing antibodies or the antagonist protein myostatin, render myoblasts refractory to HDAC inhibitors. Muscles from animals treated with the HDAC inhibitor trichostatin A display increased production of follistatin and enhanced expression of markers of regeneration following muscle injury. These data identify follistatin as a central mediator of the fusigenic effects exerted by deacetylase inhibitors on skeletal muscles and establish a rationale for their use to manipulate skeletal myogenesis and promote muscle regeneration.
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Base de dados:
MEDLINE
Assunto principal:
Proteínas Nucleares
/
Músculo Esquelético
/
Fibras Musculares Esqueléticas
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Mioblastos Esqueléticos
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Folistatina
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Inibidores de Histona Desacetilases
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Female
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Humans
Idioma:
En
Ano de publicação:
2004
Tipo de documento:
Article