Department of Emergency, Changhai Hospital, Second Military Medical University, Shanghai, China.
Eur Rev Med Pharmacol Sci. 2013 Nov;17(21):2867-73.
Skeletal muscle transcriptome of patients with sepsis was compared with that of controls to elucidate the molecular mechanisms underlying sepsis-induced skeletal muscle dysfunction.
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).
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.
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.
比较脓毒症患者的骨骼肌转录组与对照组，阐明脓毒症引起的骨骼肌功能障碍的分子机制。
从基因表达数据库（GEO）下载基因表达数据集 GSE13205，其中包括 13 个脓毒症样本和 8 个对照。采用 t 检验筛选差异表达基因（DEGs）。使用 UCSC 信息为 DEGs 构建转录调控网络。为了识别脓毒症中改变的生物学功能，使用 DAVID 对网络中的所有基因进行通路富集分析。此外，使用 Connectivity Map（camp）检索相关的小分子。
在脓毒症中获得了 287 个差异表达基因，其中 149 个上调，138 个下调。然后构建了一个包含 83 个节点和 98 个边的转录调控网络。获得了 5 个转录因子（TFs）及其靶基因。显著改变的生物学途径包括胰岛素信号通路、神经营养因子信号通路、果糖和甘露糖代谢、昼夜节律和细胞凋亡。此外，还获得了一些相关的分子，如曲唑酮和他普西龙。
本研究深入了解了脓毒症及相关骨骼肌功能障碍的分子变化。这些信息有助于揭示发病机制并开发有效的治疗方法。
