signature=6fc8695e893a0ded735ca5e4200af72c,Exercise and sActRIIB-Fc affects molecular signature of s...

摘要：

Duchenne Muscular Dystrophy (DMD) is characterized by progressive wasting of skeletal muscle. Soluble Activin receptor Fc (sActRIIB-Fc) or placebo (PBS) was injected 1x/wk to block myostatin/activins with or without voluntary running exercise in young mdx mice, a model of DMD. C57Bl/10ScSnJ mice acted as healthy controls. In a 7- week experiment, sActRIIB-Fc increased muscle mass while exercise enhanced muscle aerobic capacity (e.g. citrate synthase and SDH activities). Microarray analysis was conducted from gastrocnemius muscle. Gene Set Enrichment (GSEA) analysis revealed that many pathways for aerobic metabolism were in the top 10 of the most downregulated gene sets in mdx muscle (FDR<0.005). However, most of these were upregulated by exercise (FDR<0.05). sActRIIB-Fc activated 92 canonical processes/pathways in active mice (sActRIIB-Fc running vs. PBS running), but only one process in sedentary mice (sActRIIB-Fc vs. PBS) (FDR<0.05). The interaction effect of sActRIIB-Fc and exercise was also shown in a protein level by analyzing different proteins by western blotting (e.g. major urinary proteins and the phosphorylation of Stat5). We report here that exercise can modulate aerobic gene expression profiles or pathways of a dystrophic muscle towards a state of a healthier muscle. Furthermore, ActRIIB-Fc, a myostatin/activin blocker affects differently in exercised and non-exercised muscles.

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