关键词: 脊髓损伤, 差异表达基因, 生物信息学分析, DAVID分析, 炎症, KEGG途径, 微阵列分析, 转录因子, 神经再生

Abstract:

Gene spectrum analysis has shown that gene expression and signaling pathways change dramatically after spinal cord injury, which may affect the microenvironment of the damaged site. Microarray analysis provides a new opportunity for investigating diagnosis, treatment, and prognosis of spinal cord injury. However, differentially expressed genes are not consistent among studies, and many key genes and signaling pathways have not yet been accurately studied. GSE5296 was retrieved from the Gene Expression Omnibus DataSet. Differ¬entially expressed genes were obtained using R/Bioconductor software (expression changed at least two-fold; P < 0.05). Database for Annotation, Visualization and Integrated Discovery was used for functional annotation of differentially expressed genes and Animal Transcription Factor Database for predicting potential transcription factors. The resulting transcription regulatory protein interaction network was mapped to screen representative genes and investigate their diagnostic and therapeutic value for disease. In total, this study identified 109 genes that were upregulated and 30 that were downregulated at 0.5, 4, and 24 hours, and 3, 7, and 28 days after spinal cord injury. The number of downregulated genes was smaller than the number of upregulated genes at each time point. Database for Annota¬tion, Visualization and Integrated Discovery analysis found that many inflammation-related pathways were upregulated in injured spinal cord. Additionally, expression levels of these inflammation-related genes were maintained for at least 28 days. Moreover, 399 regulation modes and 77 nodes were shown in the protein-protein interaction network of upregulated differentially expressed genes. Among the 10 upregulated differentially expressed genes with the highest degrees of distribution, six genes were transcription factors. Among these tran¬scription factors, ATF3 showed the greatest change. ATF3 was upregulated within 30 minutes, and its expression levels remained high at 28 days after spinal cord injury. These key genes screened by bioinformatics tools can be used as biological markers to diagnose diseases and provide a reference for identifying therapeutic targets.

Key words: nerve regeneration, spinal cord injury, differentially expressed genes, bioinformatics analyses, Database for Annotation, Visualization and Integrated Discovery analysis, inflammation, Kyoto Encyclopedia of Genes and Genomes pathway, microarray, transcription factors, neural regeneration