title: Glucocorticoid-induced leucine zipper (GILZ) and long GILZ inhibit myogenic differentiation and mediate anti-myogenic effects of glucocorticoids.
abstract: 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.
authors.affiliation: Dipartimento di Medicina Clinica e Sperimentale, Sezione di Farmacologia, Tossicologia e Chemioterapia, Universitá di Perugia, 06122 Perugia, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Bruscoli
authors.forename: Valerio
authors.initials: V
authors.lastname: Donato
authors.forename: Enrico
authors.initials: E
authors.lastname: Velardi
authors.forename: Moises
authors.initials: M
authors.lastname: Di Sante
authors.forename: Graziella
authors.initials: G
authors.lastname: Migliorati
authors.forename: Rosario
authors.initials: R
authors.lastname: Donato
authors.forename: Carlo
authors.initials: C
authors.lastname: Riccardi
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D003907:Dexamethasone / Q000494:pharmacology*; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D018507:Gene Expression Regulation, Developmental; D005938:Glucocorticoids / Q000494:pharmacology*; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D024510:Muscle Development / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D018008:Myogenin / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: C498608:Dsip1 protein, mouse; D005938:Glucocorticoids; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D018008:Myogenin; D020033:Protein Isoforms; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014157:Transcription Factors; D003907:Dexamethasone; D008156:Luciferases