Comparative gene expression profiling reveals key pathways in septic skeletal muscle.

AIM: Skeletal muscle transcriptome of patients with sepsis was compared with that of controls to elucidate the molecular mechanisms underlying sepsis-induced skeletal muscle dysfunction. MATERIALS AND METHODS: Gene expression data set GSE13205 was downloaded from Gene Expression Omnibus (GEO), including 13 septic samples and 8 controls. Differentially expressed genes (DEGs) were screened out with t-test. Transcriptional regulatory network was constructed for the DEGs with information from UCSU. In order to identify altered biological functions in sepsis, pathway enrichment analysis was conducted for all the genes in the network with DAVID. Besides, relevant small molecules were retrieved using the Connectivity Map (camp). RESULTS: A total of 287 DEGs were obtained in sepsis, 149 up-regulated and 138 down-regulated. A transcriptional regulatory network containing 83 nodes and 98 edges was then constructed. Five transcription factors (TFs) and their target genes were acquired. Significantly altered biological pathways included insulin signaling pathway, neurotrophin signaling pathway, fructose and mannose metabolism, circadian rhythm and apoptosis. Besides, a number of relevant molecules were obtained, such as trazodone and thapsigargin. CONCLUSIONS: Our study provided an insight into the molecular changes sepsis and related skeletal muscle dysfunction. The information could be beneficial in disclosing the pathogenesis and developing effective therapies.