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Further insight into molecular mechanism underlying thoracic spinal cord injury using bioinformatics methods

机译:使用生物信息学方法进一步了解胸椎脊髓损伤的分子机制

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摘要

The present study aimed to explore the molecular mechanisms underlying the development of thoracic spinal cord injury (SCI). The gene expression profile of , which included 12 thoracic non-injured spinal cord control samples and 12 thoracic transected spinal cord samples at different stages of SCI, was obtained from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified using the limma package in R/Bioconductor. DEG-associated pathways were analyzed using the Kyoto encyclopedia of genes and genomes database. A protein-protein interaction (PPI) network was constructed and transcription factors (TFs) were predicted using cytoscape. Compared with the control samples, there were 1,942, 396, 188 and 396 DEGs identified at day 3 (d3), week 1 (wk1), wk2 and month 1 (m1), respectively. Cluster analysis indicated that the DEGs at m1 were similar to those in the control group. Downregulated DEGs were enriched in nervous system disease pathways, such as Parkinson's disease. Upregulated DEGs were enriched in immune response-associated pathways, such as Fc γ R-mediated phagocytosis at early stages (d3 and wk1). Upregulated DEGs were enriched in pathways associated with cancer and pyrimidine metabolism at wk2 and m1, respectively. In the PPI network, nodes including RAC2, CD4, STAT3 and JUN were identified. Furthermore, ATF3, JUN and EGR1 were identified as TFs associated with SCI. In conclusion, the results of the present study showed that the number of DEGs decreased in a time-dependent manner following SCI. OLIG1, ATF3 and JUN may represent SCI regeneration-associated genes. Immune-associated inflammation was shown to be important in SCI, and SCI exhibits causal associations with other diseases, including cardiovascular disease and cancers. The present study provided novel insight into the molecular mechanisms of SCI regeneration, which may aid in the development of strategies to enhance recovery following SCI.
机译:本研究旨在探讨胸脊髓损伤(SCI)发展的分子机制。从Gene Expression Omnibus数据库中获得了的基因表达谱,其中包括12个SCI不同阶段的胸部未损伤脊髓对照样品和12个经胸椎横断的脊髓样品。使用R / Bioconductor中的limma软件包鉴定了差异表达的基因(DEG)。使用京都百科全书的基因和基因组数据库分析了与DEG相关的途径。构建了蛋白质-蛋白质相互作用(PPI)网络,并使用cytoscape预测了转录因子(TFs)。与对照样品相比,在第3天(d3),第1周(wk1),wk2和第1月(m1)分别确定了1,942、396、188和396个DEG。聚类分析表明,m1处的DEG与对照组相似。下调的DEG富含神经系统疾病途径,如帕金森氏病。上调的DEG富含免疫反应相关的途径,例如在早期阶段(d3和wk1)由FcγR介导的吞噬作用。上调的DEG分别富含与癌症和嘧啶代谢有关的途径,分别位于wk2和m1。在PPI网络中,已识别出包括RAC2,CD4,STAT3和JUN的节点。此外,ATF3,JUN和EGR1被确定为与SCI相关的TF。总之,本研究的结果表明,SCI后DEG的数量以时间依赖的方式减少。 OLIG1,ATF3和JUN可能代表SCI再生相关基因。免疫相关的炎症在SCI中很重要,SCI与其他疾病(包括心血管疾病和癌症)之间存在因果关系。本研究提供了SCI再生的分子机制的新见解,这可能有助于发展战略,以增强SCI后的恢复。

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