Pharmacological inhibition of REV-ERB stimulates differentiation, inhibits turnover and reduces fibrosis in dystrophic muscle.
Pharmacological inhibition of REV-ERB stimulates differentiation, inhibits turnover and reduces fibrosis in dystrophic muscle.
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DOI：
10.1038/s41598-017-17496-7
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发表时间：
2017-12-07
影响因子：
4.6
通讯作者：
Flaveny CA
中科院分区：
文献类型：
--
作者：
Welch RD;Billon C;Valfort AC;Burris TP;Flaveny CA
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 injury. Therefore, we decided to explore whether the REV-ERB antagonist SR8278 could slow the progression of muscular dystrophy. In mdx mice SR8278 increased lean mass and muscle function, and decreased muscle fibrosis and muscle protein degradation. Interestingly, we also found that SR8278 increased the SC pool through stimulation of Notch and Wnt signaling. These results suggest that REV-ERB is a potent target for the treatment of DMD.
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影响因子：
14.9
作者：
Burke, L;Downes, M;Muscat, GEO
通讯作者：
Muscat, GEO
影响因子：
3.7
作者：
Crumbley C;Burris TP
通讯作者：
Burris TP
影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.2147/dddt.s97635
发表时间：
2017
期刊：
Drug design, development and therapy
影响因子：
--
作者：
Lim KR;Maruyama R;Yokota T
通讯作者：
Yokota T
影响因子：
4.5
作者：
Chalkiadaki A;Igarashi M;Nasamu AS;Knezevic J;Guarente L
通讯作者：
Guarente L