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.
Deacetylase inhibitors increase muscle cell size by promoting myoblast recruitment and fusion through induction of follistatin / S. Iezzi, M. Di Padova, C. Serra, G. Caretti, C. Simone, E. Maklan, G. Minetti, P. Zhao, E.P. Hoffman, P.L. Puri, V. Sartorelli. - In: DEVELOPMENTAL CELL. - ISSN 1534-5807. - 6:5(2004), pp. 673-684.
|Titolo:||Deacetylase inhibitors increase muscle cell size by promoting myoblast recruitment and fusion through induction of follistatin|
|Data di pubblicazione:||2004|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/S1534-5807(04)00107-8|
|Appare nelle tipologie:||01 - Articolo su periodico|