Xu Feng, Gao Feng, Liu Yadong, Wang Zhenyu, Zhuang Xinming, Qu Zhigang, Ma Hui, Liu Yi, Fu Changfeng, Zhang Qi, Duan Xiaoying
Department of Spine Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
Department of Orthopaedics, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.
Mol Med Rep. 2016 Mar;13(3):2925-31. doi: 10.3892/mmr.2016.4861. Epub 2016 Feb 4.
The present study aimed to explore the molecular mechanisms associated with intervertebral disc degeneration (IDD) induced by tumor necrosis factor (TNF)‑α and interleukin (IL)‑1β. The microarray dataset no. GSE42611 was downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) between four experimental nucleus pulposus samples and four control nucleus pulposus samples were analyzed. Subsequently, Gene Ontology (GO) and pathway enrichment analyses of DEGs were performed, followed by protein‑protein interaction (PPI) network construction and prediction of a regulatory network of transcription factor (TFs). Finally, the transcriptional regulatory network was integrated into the PPI network to analyze the network modules. A total of 246 upregulated and 290 downregulated DEGs were identified. The upregulated DEGs were mainly associated with GO terms linked with inflammatory response and apoptotic pathways, while the downregulated DEGs were mainly associated with GO terms linked with cell adhesion and pathways of extracellular matrix ‑ receptor interaction. In the PPI network, IL6, COL1A1, NFKB1 and HIF1A were hub genes, and in addition, NFKB1 and HIF1A were TFs. Pathways of apoptosis and extracellular matrix ‑ receptor interaction may have important roles in IDD progression. IL6, COL1A1 and the TFs NFKB1 and HIF1A may be used as biomarkers for IDD diagnosis and treatment.
本研究旨在探讨与肿瘤坏死因子(TNF)-α和白细胞介素(IL)-1β诱导的椎间盘退变(IDD)相关的分子机制。从基因表达综合数据库下载了编号为GSE42611的微阵列数据集。分析了四个实验性髓核样本和四个对照髓核样本之间的差异表达基因(DEG)。随后,对DEG进行基因本体(GO)和通路富集分析,接着构建蛋白质-蛋白质相互作用(PPI)网络并预测转录因子(TF)调控网络。最后,将转录调控网络整合到PPI网络中以分析网络模块。共鉴定出246个上调的DEG和290个下调的DEG。上调的DEG主要与与炎症反应和凋亡途径相关的GO术语有关,而下调的DEG主要与与细胞粘附和细胞外基质-受体相互作用途径相关的GO术语有关。在PPI网络中,IL6、COL1A1、NFKB1和HIF1A是枢纽基因,此外,NFKB1和HIF1A是TF。凋亡和细胞外基质-受体相互作用途径可能在IDD进展中起重要作用。IL6、COL1A1以及TF NFKB1和HIF1A可作为IDD诊断和治疗的生物标志物。