C/EBPβ regulates dexamethasone‐induced muscle cell atrophy and expression of atrogin‐1 and MuRF1

Abstract

Muscle wasting in catabolic patients is in part mediated by glucocorticoids and is associated with increased expression and activity of the transcription factor C/EBPβ. It is not known, however, if C/EBPβ is causally linked to glucocorticoid-induced muscle atrophy. We used dexamethasone-treated L6 myoblasts and myotubes to test the role of C/EBPβ in glucocorticoid-induced expression of the muscle-specific ubiquitin ligases atrogin-1 and MuRF1, protein degradation, and muscle atrophy by transfecting cells with C/EBPβ siRNA. In myoblasts, silencing C/EBPβ expression with siRNA inhibited dexamethasone-induced increase in protein degradation, atrogin-1 and MuRF1 expression, and muscle cell atrophy. Similar effects of C/EBPβ siRNA were seen in myotubes except that the dexamethasone-induced increase in MuRF1 expression was not affected by C/EBPβ siRNA in myotubes. In additional experiments, overexpressing C/EBPβ did not influence atrogin-1 or MuRF1 expression in myoblasts or myotubes. Taken together, our observations suggest that glucocorticoid-induced muscle wasting is at least in part regulated by C/EBPβ. Increased C/EBPβ expression alone, however, is not sufficient to upregulate atrogin-1 and MuRF1 expression.