| First Author | Xiong X | Year | 2021 |
| Journal | Exp Cell Res | Volume | 406 |
| Issue | 2 | Pages | 112766 |
| PubMed ID | 34364881 | Mgi Jnum | J:328102 |
| Mgi Id | MGI:6789297 | Doi | 10.1016/j.yexcr.2021.112766 |
| Citation | Xiong X, et al. (2021) Inhibition of Rev-erbalpha ameliorates muscular dystrophy. Exp Cell Res 406(2):112766 |
| abstractText | Duchene muscular dystrophy leads to progressive muscle structural and functional decline due to chronic degenerative-regenerative cycles. Enhancing the regenerative capacity of dystrophic muscle provides potential therapeutic options. We previously demonstrated that the circadian clock repressor Rev-erbalpha inhibited myogenesis and Rev-erbalpha ablation enhanced muscle regeneration. Here we show that Rev-erbalpha deficiency in the dystrophin-deficient mdx mice promotes regenerative myogenic response to ameliorate muscle damage. Loss of Rev-erbalpha in mdx mice improved dystrophic pathology and muscle wasting. Rev-erbalpha-deficient dystrophic muscle exhibit augmented myogenic response, enhanced neo-myofiber formation and attenuated inflammatory response. In mdx myoblasts devoid of Rev-erbalpha, myogenic differentiation was augmented together with up-regulation of Wnt signaling and proliferative pathways, suggesting that loss of Rev-erbalpha inhibition of these processes contributed to the improvement in regenerative myogenesis. Collectively, our findings revealed that the loss of Rev-erbalpha function protects dystrophic muscle from injury by promoting myogenic repair, and inhibition of its activity may have therapeutic utilities for muscular dystrophy. |
