Glucocorticoid-Induced Leucine Zipper (GILZ) and Long GILZ Inhibit Myogenic Differentiation and Mediate Anti-myogenic Effects of Glucocorticoids

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)areimportantregulators 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 myotubes formation while GILZ and L-GILZ silencing dampened GC effects. Inhibition of differentiation caused by GILZ/L-GILZ over-expression 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.