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

Simona Iezzi, Monica Di Padova, Carlo Serra, Giuseppina Caretti, Cristiano Simone, Eric Maklan, Giulia Minetti, Po Zhao, Eric P. Hoffman, Pier Lorenzo Puri, Vittorio Sartorelli

Research output: Contribution to journalArticle

163 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)673-684
Number of pages12
JournalDevelopmental Cell
Volume6
Issue number5
DOIs
Publication statusPublished - May 2004

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Follistatin
Myoblasts
Cell Size
Muscle Cells
Muscle
Fusion reactions
Cells
Skeletal Muscle Fibers
Muscles
Histone Deacetylase Inhibitors
Muscle Development
Regeneration
trichostatin A
Myostatin
RNA Interference
Neutralizing Antibodies
Insulin-Like Growth Factor I
Interleukin-4
Skeletal Muscle
Refractory materials

ASJC Scopus subject areas

  • Developmental Biology

Cite this

Deacetylase inhibitors increase muscle cell size by promoting myoblast recruitment and fusion through induction of follistatin. / Iezzi, Simona; Di Padova, Monica; Serra, Carlo; Caretti, Giuseppina; Simone, Cristiano; Maklan, Eric; Minetti, Giulia; Zhao, Po; Hoffman, Eric P.; Puri, Pier Lorenzo; Sartorelli, Vittorio.

In: Developmental Cell, Vol. 6, No. 5, 05.2004, p. 673-684.

Research output: Contribution to journalArticle

Iezzi, S, Di Padova, M, Serra, C, Caretti, G, Simone, C, Maklan, E, Minetti, G, Zhao, P, Hoffman, EP, Puri, PL & Sartorelli, V 2004, 'Deacetylase inhibitors increase muscle cell size by promoting myoblast recruitment and fusion through induction of follistatin', Developmental Cell, vol. 6, no. 5, pp. 673-684. https://doi.org/10.1016/S1534-5807(04)00107-8
Iezzi, Simona ; Di Padova, Monica ; Serra, Carlo ; Caretti, Giuseppina ; Simone, Cristiano ; Maklan, Eric ; Minetti, Giulia ; Zhao, Po ; Hoffman, Eric P. ; Puri, Pier Lorenzo ; Sartorelli, Vittorio. / Deacetylase inhibitors increase muscle cell size by promoting myoblast recruitment and fusion through induction of follistatin. In: Developmental Cell. 2004 ; Vol. 6, No. 5. pp. 673-684.
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