Melhora funcional e patológica de camundongos com distrofia muscular e superexpressão do gene nuclear gama relacionado a estrógenos
USA – pesquisadores identificaram em camundongos com distrofia muscular uma significativa redução da expressão do gene gene nuclear gama relacionado a estrógenos. O aumento da expressão deste gene em camundongos promoveu uma melhora da tolerância ao exercício e redução de alterações patológicas. Apesar de não haver nenhuma alteração da expressão das proteínas da membrana muscular houve uma redução do stress oxidativo e aumento da angiogênese, Drogas que aumentem a expressão do gene gene nuclear gama relacionado a estrógenos poderiam retardar a evolução da doença.
O resumo em inglês pode ser lido abaixo:
(FASEB J, Jun 2013; 10.1096/fj.13-228296) Muscle ERR mitigates Duchenne muscular dystrophy via metabolic and angiogenic reprogramming
Antonios Matsakas, Vikas Yadav, Sabina Lorca, and Vihang Narkar -USA
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-γ (ERRγ), 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 ERRγ selectively in the dystrophic muscles of the mdx mice restored metabolic and angiogenic gene expression compared with control mdx mice. Further, ERRγ enhanced muscle oxidative myofibers, vasculature, and blood flow (by 33–66%) and improved exercise tolerance (by 75%) in the dystrophic mice. Restoring muscle ERRγ pathway ameliorated muscle damage and also prevented DMD hallmarks of postexercise muscle damage, hypoxia, and fatigue in mdx mice. Notably, ERRγ did not restore sarcolemmal DAG complex, which is thus dispensable for antidystrophic effects of ERRγ. In summary, ERRγ-dependent metabolic and angiogenic gene program is defective in DMD, and we demonstrate that its restoration is a potential strategy for treating muscular dystrophy.
