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Deacetylase inhibitors increase muscle cell size by promoting myoblast recruitment and fusion through induction of follistatin.

Authors :
Iezzi S
Di Padova M
Serra C
Caretti G
Simone C
Maklan E
Minetti G
Zhao P
Hoffman EP
Puri PL
Sartorelli V
Source :
Developmental cell [Dev Cell] 2004 May; Vol. 6 (5), pp. 673-84.
Publication Year :
2004

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.

Details

Language :
English
ISSN :
1534-5807
Volume :
6
Issue :
5
Database :
MEDLINE
Journal :
Developmental cell
Publication Type :
Academic Journal
Accession number :
15130492
Full Text :
https://doi.org/10.1016/s1534-5807(04)00107-8