Long Non-Coding RNA Regulates GDF5 Expression in Denervated Mouse Skeletal Muscle.

Skeletal muscle is a highly plastic tissue and decreased skeletal muscle mass (muscle atrophy) results in deteriorated motor function and perturbed body homeostasis. promoter-associated long non-coding RNA (lncRNA) promotes skeletal muscle atrophy caused by surgical denervation; however, the precise molecular mechanism remains unclear. Here, we examined the downstream genes of during muscle atrophy following denervation of tibialis anterior (TA) muscles in C57BL/6J mice. knockdown affected the expression of 848 genes. Sixty-five of the genes differentially regulated by knockdown coded secretory proteins. Among these 65 genes identified in -depleted skeletal muscles after denervation, we focused on the increased expression of growth/differentiation factor 5 (GDF5), an inhibitor of muscle atrophy. 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 also revealed that regulated differential gene expression between myogenic differentiation and muscle atrophy. This is the first report demonstrating the in vivo role of 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.