Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 285, Issue 14, Pages 10385-10396Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M109.070136
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Funding
- Associazione Italiana per la Ricerca sul Cancro Milan
- Ministero Istruzione Universita della Ricerca
- Fondo per gli Investimenti della Ricerca di Base [RBPR05NWWC CHEM-PROFARMA-NET]
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Myogenesis is a process whereby myoblasts differentiate and fuse into multinucleated myotubes, the precursors of myofibers. Various signals and factors modulate this process, and glucocorticoids (GCs) are important regulators of skeletal muscle metabolism. We show that glucocorticoid-induced leucine zipper (GILZ), a GC-induced gene, and the newly identified isoform long GILZ (L-GILZ) are expressed in skeletal muscle tissue and in C2C12 myoblasts where GILZ/L-GILZ maximum expression occurs during the first few days in differentiation medium. Moreover, we observed that GC treatment of myoblasts, which increased GILZ/L-GILZ expression, resulted in reduced myotube formation, whereas GILZ and L-GILZ silencing dampened GC effects. Inhibition of differentiation caused by GILZ/L-GILZ overexpression correlated with inhibition of MyoD function and reduced expression of myogenin. Notably, results indicate that GILZ and L-GILZ bind and regulate MyoD/HDAC1 transcriptional activity, thus mediating the anti-myogenic effect of GCs.
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