Fbxw7 beta is an inducing mediator of dexamethasone-induced skeletal muscle atrophy in vivo with the axis of Fbxw7 beta-myogenin-atrogenes

Abstract

Muscle atrophy is induced by several pathways, e.g., it can be attributed to inherited cachectic symptoms, genetic disorders, sarcopenia, or chronic side effects of treatments. However, the underlying regulatory mechanisms that contribute to muscle atrophy have not been fully elucidated. In this study, we evaluated the role of Fbxw7 beta, an ubiquitin E3 ligase, in a dexamethasone-induced muscle atrophy model. In this model, endogenous Fbxw7 beta was up-regulated; furthermore, the Fbxw7 beta-myogenin-atrogene axis was upregulated, supporting our previous results linking Fbxw7 beta to muscle atrophy in vitro. Also, muscle atrophy was associated with the Fbxw7 beta-myogenin-atrogene axis and the down-regulation of Dach2, a repressor of myogenin. Taken together, these results suggest that the ubiquitin E3 ligase Fbxw7 beta and the Fbxw7 beta-myogenin-atrogene axis have important roles in a dexamethasone-induced muscle atrophy model in vivo and in vitro. Additionally, the Fbxw7 beta-Dach2-myogenin-atrogene axis is a potential mechanism underlying muscle atrophy in cases of abnormal Fbxw7 beta expression-induced muscle atrophy or myogenic degenerative disease.