Dipartimento di Medicina Clinica e Sperimentale, Sezione di Farmacologia, Tossicologia e Chemioterapia, Universitá di Perugia, 06122 Perugia, Italy.
J Biol Chem. 2010 Apr 2;285(14):10385-96. doi: 10.1074/jbc.M109.070136. Epub 2010 Feb 2.
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.
成肌分化是一个肌母细胞分化并融合形成多核肌管的过程，肌管是肌纤维的前体。各种信号和因子调节这个过程，而糖皮质激素（GCs）是骨骼肌代谢的重要调节剂。我们发现，糖皮质激素诱导亮氨酸拉链（GILZ），一种 GC 诱导基因，和新鉴定的长 GILZ（L-GILZ）异构体，在骨骼肌组织和 C2C12 成肌细胞中表达，GILZ/L-GILZ 的最大表达发生在分化培养基中的最初几天。此外，我们观察到，GC 处理成肌细胞，增加了 GILZ/L-GILZ 的表达，导致肌管形成减少，而 GILZ 和 L-GILZ 的沉默减弱了 GC 的作用。GILZ/L-GILZ 过表达引起的分化抑制与 MyoD 功能的抑制和肌生成素表达的降低有关。值得注意的是，结果表明 GILZ 和 L-GILZ 结合并调节 MyoD/HDAC1 的转录活性，从而介导 GCs 的抗肌生成作用。
