Pharmacological inhibition of REV-ERB stimulates differentiation, inhibits turnover and reduces fibrosis in dystrophic muscle.

ABSTRACT: Duchenne muscular dystrophy (DMD) is a debilitating X-linked disorder that is fatal. DMD patients lack the expression of the structural protein dystrophin caused by mutations within the DMD gene. The absence of functional dystrophin protein results in excessive damage from normal muscle use due to the compromised structural integrity of the dystrophin associated glycoprotein complex. As a result, DMD patients exhibit ongoing cycles of muscle destruction and regeneration that promote inflammation, fibrosis, mitochondrial dysfunction, satellite cell (SC) exhaustion and loss of skeletal and cardiac muscle function. The nuclear receptor REV-ERB suppresses myoblast differentiation and recently we have demonstrated that the REV-ERB antagonist, SR8278, stimulates muscle regeneration after acute i

SUBMITTER: Welch RD 

PROVIDER: S-EPMC5719458 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature