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Deacetylase inhibitors increase muscle cell size by promoting myoblast recruitment and fusion through induction of follistatin.
- 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.
- Subjects :
- Animals
Antibodies pharmacology
Cell Differentiation drug effects
Cell Differentiation genetics
Cyclic AMP Response Element-Binding Protein
DNA-Binding Proteins metabolism
Enzyme Inhibitors pharmacology
Enzyme Inhibitors therapeutic use
Female
Follistatin genetics
Follistatin metabolism
Histone Deacetylases metabolism
Humans
Hydroxamic Acids pharmacology
Membrane Fusion genetics
Mice
Muscle Fibers, Skeletal cytology
Muscle Fibers, Skeletal drug effects
Muscle, Skeletal cytology
Muscle, Skeletal enzymology
MyoD Protein metabolism
Myoblasts, Skeletal cytology
Myoblasts, Skeletal drug effects
NFATC Transcription Factors
NIH 3T3 Cells
RNA Interference
Regeneration drug effects
Regeneration genetics
Transcription Factors metabolism
Follistatin antagonists & inhibitors
Histone Deacetylase Inhibitors
Muscle Fibers, Skeletal enzymology
Muscle, Skeletal growth & development
Myoblasts, Skeletal enzymology
Nuclear Proteins
Subjects
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