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Myostatin regulates fate of satellite cells in dystrophic muscle
The goal of this proposal is to determine whether myostatin, expressed in both skeletal muscle and fibroblasts, regulates the conversion of satellite cells to fibroblasts and whether this conversion contributes to fibrosis prominent in dystrophic muscle. First, we will determine the ability of myostatin to induce the conversion of satellite cells to fibroblasts in an animal model of dystrophic muscle. Second, we will investigate the ability of myostatin to induce fibrogenic converfsion of human satellite cells isolated from both normal and muscular dystrophy subjects. Third, we will investigate whether cross-talk between myostatin signaling and wnt signaling, which stimulates stem cell differentiation into myogenic lineage is involved int eh conversion of muscle satellite cells from a myogenic to fibrogenic lineage. The knowledge obtained by this study will be important in the application of new myostatin inhibitors currently in trials for muscular dystrophy.