Transcriptome sequencing and analysis reveals the molecular mechanism of skeletal muscle atrophy induced by denervation.

Abstract

Background\nThe molecular mechanism of denervated muscle atrophy is very complex and has not been elucidated to date. In this study, we aimed to use transcriptome sequencing technology to systematically analyze the molecular mechanism of denervated muscle atrophy in order to eventually develop effective strategies or drugs to prevent muscle atrophy.\n\n\nMethods\nTranscriptome sequencing technology was used to analyze the differentially expressed genes (DEGs) in denervated skeletal muscles. Unsupervised hierarchical clustering of DEGs was performed. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was used to analyze the DEGs.\n\n\nResults\nResults showed that 2,749 transcripts were up-regulated, and 2,941 transcripts were down-regulated in denervated tibialis anterior (TA) muscles after 14 days of denervation. The up-regulated expressed genes were analyzed through GO and the results demonstrated that biological processes of the up-regulated expressed genes included apoptotic process, cellular response to DNA damage stimulus, aging, and protein ubiquitination; the cellular component of the up-regulated expressed genes included cytoplasm, cytoskeleton, and nucleus; and the molecular function of the up-regulated expressed genes included ubiquitin-protein transferase activity and hydrolase activity. The KEGG pathway of the up-regulated expressed genes included ubiquitin mediated proteolysis, Fc gamma R-mediated phagocytosis, and transforming growth factor-beta (TGF-β) signaling pathway. The biological processes of the down-regulated expressed genes included angiogenesis, tricarboxylic acid cycle, adenosine triphosphate (ATP) biosynthetic process, muscle contraction, gluconeogenesis; the cellular component of the down-regulated expressed genes included mitochondrion, cytoskeleton, and myofibril; and the molecular function of the down-regulated expressed genes included nicotinamide adenine dinucleotide plus hydrogen (NADH) dehydrogenase (ubiquinone) activity, proton-transporting ATP synthase activity, ATP binding, electron carrier activity, cytochrome-c oxidase activity, and oxidoreductase activity. The KEGG pathway of the down-regulated expressed genes included oxidative phosphorylation, tricarboxylic acid cycle, glycolysis/gluconeogenesis, and the PI3K-Akt signaling pathway.\n\n\nConclusions\nA huge number of DEGs were identified in TA muscles after denervation. The up-regulated expressed genes mainly involve in proteolysis, apoptosis, and ageing. The down-regulated expressed genes mainly involve in energy metabolism, angiogenesis, and protein synthesis. This study further enriched the molecular mechanism of denervation-induced muscle atrophy.