HDAC8 regulates canonical Wnt pathway to promote differentiation in skeletal muscles

Luca Ferrari, Cinzia Bragato, Loredana Brioschi, Marco Spreafico, Simona Esposito, Alex Pezzotta, Fabrizio Pizzetti, Artal Moreno-Fortuny, Gianfranco Bellipanni, Antonio Giordano, Paola Riva, Flavia Frabetti, Paola Viani, Giulio Cossu, Marina Mora, Anna Marozzi, Anna Pistocchi

Research output: Contribution to journalArticlepeer-review

Abstract

Histone deacetylase 8 (HDAC8) is a class 1 histone deacetylase and a member of the cohesin complex. HDAC8 is expressed in smooth muscles, but its expression in skeletal muscle has not been described. We have shown for the first time that HDAC8 is expressed in human and zebrafish skeletal muscles. Using RD/12 and RD/18 rhabdomyosarcoma cells with low and high differentiation potency, respectively, we highlighted a specific correlation with HDAC8 expression and an advanced stage of muscle differentiation. We inhibited HDAC8 activity through a specific PCI-34051 inhibitor in murine C2C12 myoblasts and zebrafish embryos, and we observed skeletal muscles differentiation impairment. We also found a positive regulation of the canonical Wnt signaling by HDAC8 that might explain muscle differentiation defects. These findings suggest a novel mechanism through which HDAC8 expression, in a specific time window of skeletal muscle development, positively regulates canonical Wnt pathway that is necessary for muscle differentiation.

Original languageEnglish
JournalJournal of Cellular Physiology
DOIs
Publication statusAccepted/In press - Jan 1 2018

Keywords

  • histone deacetylase 8 (HDAC8)
  • rhabdomyosarcoma
  • skeletal muscle
  • Wnt
  • zebrafish

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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