Abstract
The molecular mechanism of muscle atrophy has been studied a lot, but there is no comprehensive analysis focusing on the denervated muscle atrophy. The gene network that controls the development of denervated muscle atrophy needs further elucidation. We examined differentially expressed genes (DEGs) from five denervated muscle atrophy microarray datasets and predicted microRNAs that target these DEGs. We also included the differentially expressed microRNAs datasets of denervated muscle atrophy in previous studies as background information to identify potential key microRNAs. Finally, we compared denervated muscle atrophy with disuse muscle atrophy caused by other reasons, and obtained the Den-genes which only differentially expressed in denervated muscle atrophy. In this meta-analysis, we obtained 429 up-regulated genes, 525 down-regulated genes and a batch of key microRNAs in denervated muscle atrophy. We found eight important microRNA-mRNA interactions (miR-1/Jun, miR-1/Vegfa, miR-497/Vegfa, miR-23a/Vegfa, miR-206/Vegfa, miR-497/Suclg1, miR-27a/Suclg1, miR-27a/Mapk14). The top five KEGG pathways enriched by Den-genes are Insulin signaling pathway, T cell receptor signaling pathway, MAPK signaling pathway, Toll-like receptor signaling pathway and B cell receptor signaling pathway. Our research has delineated the RNA regulatory network of denervated muscle atrophy, and uncovered the specific genes and terms in denervated muscle atrophy.
Highlights
Denervated muscle atrophy refers to muscle atrophy caused by injury of nerves that innervate the muscle
The biological axis composed of histone deacetylases (HDACs) 4 and 5, transcription factors Dach[2] and myogenin can control the expression of many denervation related genes, including atrogin and MuRF119–22
We only included the data sets that denervated for 7–14 days, because the muscle with denervation greater than 7 days has entered the stage of pathological a trophy[31], and the gene expression profiles denervated for 7/14 days have high similarity, which can ensure the homogeneity of the included data sets[32]
Summary
Denervated muscle atrophy refers to muscle atrophy caused by injury of nerves that innervate the muscle. Denervated muscle atrophy is the main cause of motor function loss after peripheral nerve injury. Skeletal muscle will atrophy and fibrosis, and eventually lead to poor recovery of muscle function or even failure to recover[1,2,3]. Depletion of skeletal muscle satellite cells, changes in related protein metabolism and enzyme activities, vascular bed remodeling and regulation of myogenic factors are all important reasons for denervated muscle a trophy[5,6,7,8,9]. Up-regulated breakdown of protein in skeletal muscle is a sign of atrophy, so all potential drugs target the proteolytic system to cure or prevent a trophy[13]. Overexpression of FoxOs can induce gene expression of atrogin and MuRF1, which will eventually lead to muscle a trophy[24,25]. Considering the complexity of these processes leading to denervated muscle atrophy, the identification of genes and pathways based on meta-analysis may help to understand the underlying molecular mechanisms
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
