| Summary: | Skeletal muscle is a highly plastic tissue and decreased skeletal muscle mass (muscle atrophy) results in deteriorated motor function and perturbed body homeostasis. <i>Myogenin</i> promoter-associated long non-coding RNA (lncRNA) <i>Myoparr</i> promotes skeletal muscle atrophy caused by surgical denervation; however, the precise molecular mechanism remains unclear. Here, we examined the downstream genes of <i>Myoparr</i> during muscle atrophy following denervation of tibialis anterior (TA) muscles in C57BL/6J mice. <i>Myoparr</i> knockdown affected the expression of 848 genes. Sixty-five of the genes differentially regulated by <i>Myoparr</i> knockdown coded secretory proteins. Among these 65 genes identified in <i>Myoparr</i>-depleted skeletal muscles after denervation, we focused on the increased expression of growth/differentiation factor 5 (GDF5), an inhibitor of muscle atrophy. <i>Myoparr</i> knockdown led to activated bone morphogenetic protein (BMP) signaling in denervated muscles, as indicated by the increased levels of phosphorylated Smad1/5/8. Our detailed evaluation of downstream genes of <i>Myoparr</i> also revealed that <i>Myoparr</i> regulated differential gene expression between myogenic differentiation and muscle atrophy. This is the first report demonstrating the in vivo role of <i>Myoparr</i> in regulating BMP signaling in denervated muscles. Therefore, lncRNAs that have inhibitory activity on BMP signaling may be putative therapeutic targets for skeletal muscle atrophy.
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