Background and Aim: The aim of this study was to discover and validate novel therapeutic targets for the treatment of sepsis-induced muscle weakness using a gene set enrichment analysis approach. Methods: Publicly available sepsis-induced myopathy gene expression signatures and gene expression signatures from 107 siRNA-mediated knockdowns were analyzed using a rank-based algorithm to evaluate the similarities. This analysis provided a list of candidate human genes with similar perturbations in sepsis and siRNA knockdown that may be involved in a response to sepsis-induced myopathy. Candidate genes were validated using quantitative RT-PCR in a cecal ligation and puncture model of septic myopathy in the mouse. Results: We calculated the gene profile distances between the host responses to septic myopathy and the 107 siRNA knockdowns. Nine genes (PSIP1, TOP1, PCGF2, SRF, HIF1A, FAS, BCL11A, UPF1 and PARK7) were selected as candidate genes likely to be involved in sepsis-induced myopathy. Quantitative RT-PCR analysis in septic mice revealed that PSIP1 expression was decreased, HIF1A, FAS and UPF1 expression were increased, and the remaining genes were unchanged. Conclusion: The gene set enrichment analysis approach is an effective method to identify new genes involved in sepsis-induced myopathy. We identified PSIP1 as a factor associated with sepsis-induced muscle myopathy.
[1]Jilin Univ, Intens Care Unit, Affiliated Hosp 1, Changchun 130021, Peoples R China.
[2]Jilin Univ, Intens Care Unit, Affiliated Hosp 2, Changchun 130021, Peoples R China.
(8.0+极速模式)