| First Author | Matsakas A | Year | 2013 |
| Journal | FASEB J | Volume | 27 |
| Issue | 10 | Pages | 4004-16 |
| PubMed ID | 23781095 | Mgi Jnum | J:201176 |
| Mgi Id | MGI:5511114 | Doi | 10.1096/fj.13-228296 |
| Citation | Matsakas A, et al. (2013) Muscle ERRgamma mitigates Duchenne muscular dystrophy via metabolic and angiogenic reprogramming. FASEB J 27(10):4004-4016 |
| abstractText | Treatment of Duchenne muscular dystrophy (DMD) by replacing mutant dystrophin or restoring dystrophin-associated glycoprotein complex (DAG) has been clinically challenging. Instead, identifying and targeting muscle pathways deregulated in DMD will provide new therapeutic avenues. We report that the expression of nuclear receptor estrogen-related receptor-gamma (ERRgamma), and its metabolic and angiogenic targets are down-regulated (50-85%) in skeletal muscles of mdx mice (DMD model) vs. wild-type mice. Corelatively, oxidative myofibers, muscle vasculature, and exercise tolerance (33%) are decreased in mdx vs. wild-type mice. Overexpressing ERRgamma selectively in the dystrophic muscles of the mdx mice restored metabolic and angiogenic gene expression compared with control mdx mice. Further, ERRgamma enhanced muscle oxidative myofibers, vasculature, and blood flow (by 33-66%) and improved exercise tolerance (by 75%) in the dystrophic mice. Restoring muscle ERRgamma pathway ameliorated muscle damage and also prevented DMD hallmarks of postexercise muscle damage, hypoxia, and fatigue in mdx mice. Notably, ERRgamma did not restore sarcolemmal DAG complex, which is thus dispensable for antidystrophic effects of ERRgamma. In summary, ERRgamma-dependent metabolic and angiogenic gene program is defective in DMD, and we demonstrate that its restoration is a potential strategy for treating muscular dystrophy.-Matsakas, A., Yadav, V., Lorca, S., Narkar, V. Muscle ERRgamma mitigates Duchenne muscular dystrophy via metabolic and angiogenic reprogramming. |
