肿瘤坏死因子-α相关椎间盘退变基因表达的生物信息学分析

Bioinformatics analysis of the gene expression profile in human degenerative disc cells exposed to TNF-α

摘要:

［目的］ 研究肿瘤坏死因子-α （tumor necrosis factor-α, TNF-α） 相关退变椎间盘基因表达谱芯片数据，应用生物信息学方法挖掘 TNF-α 刺激后退变椎间盘的关键差异基因，初步探讨其相关信号通路及相互作用网络，为椎间盘退变分子机制研究提供线索。［方法］ 在公共数据库 GEO （Gene Expression Omnibus） 中下载 TNF-α 刺激后退变椎间盘的基因芯片数据，通过 R 语言筛选出 TNF-α 刺激后退变椎间盘细胞的差异表达基因，利用 DAVID、STRING 在线工具对差异表达基因进行基因本体、信号通路及相互作用网络的分析。［结果］在 TNF-α 刺激后的退变椎间盘纤维环细胞中共找到 754 条关键差异表达基因，其中上调 461 条，下调 293 条；基因本体注释分析表明这些差异表达基因主要与细胞外基质、损伤反应、炎症反应、凋亡调控等相关；信号通路分析表明这些差异表达基因主要涉及到细胞因子相互作用、凋亡、NOD 样受体、趋化因子转导等信号通路；相互作用网络分析表明 JUN、CCL3、ANHK 等基因可能在椎间盘退变中起关键作用。［结论］ 应用生物信息学方法分析 TNF-α 刺激后退变椎间盘基因表达谱发现 CCL3 等基因可能通过炎症反应在椎间盘退变的发生发展中起一定作用，生物信息学方法可发现一些潜在靶基因，为椎间盘退变的研究提供新的思路。

Abstract:

[Objective] To reveal the key differentially expressed genes and regulatory mechanisms associated with tumor necrosis fac- tor-α (TNF-α) in human degenerative intervertebral disc by analyzing microarray data using bioinformatics, and to explore the related sig- naling pathways and interactions network, providing clues for future investigations on the molecular mechanisms of disc degeneration. [Methods] The microarray data on degenerative intervertebral disc after stimulation with TNF-α were downloaded from the public data- base GEO (Gene Expression Omnibus) , to find the differential expressed genes between degenerative disc cells and those stimulated with TNF-α by a screening tool, and the analyses on gene ontology, signaling pathways and interaction networks for differentially expressed genes were conducted using DAVID, STRING and other online tools. [Results] A total of 754 key differentially expressed genes were found in degenerated annulus fibroblasts stimulated by TNF-α, of which 461 were up-regulated and 293 were down-regulated. In term of gene ontology annotation analysis, these differentially expressed genes were mainly related to extracellular matrix, injury reaction, inflammation, apoptosis regulation. In term of signal pathway analysis, these differentially expressed genes were mainly related to signal pathways such as cytokine interaction, apoptosis, NOD-like receptors, chemokine transduction. In term of interaction network analysis, genes, such as JUN, CCL3 and ANHK may play a key role in the intervertebral disc degeneration. [Conclusion] It has found that CCL3 and other genes may play a certain role in the development of disc degeneration by inflammatory reactions using bioinformatics analysis of gene expression profil- ing of degenerative intervertebral disc stimulated by TNF-α, suggesting that bioinformatics methods can find a number of potential target genes to provide new ideas for the research of degenerative intervertebral disc.