Identifying the potential role of IL-1β in the molecular mechanisms of disc degeneration using gene expression profiling and bioinformatics analysis
Ning Fan, Shuo Yuan, Yong Hai, Peng Du, Jian Li, Xiaochuan Kong, Wenyi Zhu, Yuzeng Liu, Lei Zang
Abstract
Purpose We performed a bioinformatics analysis to identify the key genes that were differentially expressed between degenerative intervertebral disc (IVD) cells with and without exposure to interleukin-1β and explore the related signaling pathways and interaction networks. Methods The microarray data were downloaded from the Gene Expression Omnibus (27,494). Then, analyses of the gene ontology, signaling pathways, and interaction networks for the differentially expressed genes (DEGs) were conducted using tools including the Database for Annotation, Visualization, and Integrated Discovery, Metascape, Gene Set Enrichment Analysis, Search Tool for the Retrieval of Interacting Genes, Cytoscape, Venn method, and packages of the R computing language. Results A total of 260 DEGs were identified, including 161 upregulated and 99 downregulated genes. Gene Ontology annotation analysis showed that these DEGs were mainly associated with the extracellular region, chemotaxis, taxis, cytokine activity, and cytokine receptor binding. A Kyoto Encyclopedia of Genes and Genomes signaling pathway analysis showed that these DEGs were mainly involved in the of cytokine-cytokine receptor interaction, rheumatoid arthritis, tumor necrosis factor signaling pathway, Salmonella infection, and chemokine signaling pathway. The interaction network analysis indicated that 10 hub genes, including CXCL8, CXCL1, CCL20, CXCL2, CXCL5, CXCL3, CXCL6, C3, PF4, and GPER1 may play key roles in IVD degeneration. Conclusions Bioinformatic analysis showed that CXCL8 and other nine key genes may play a role in the development of disc degeneration induced by inflammatory reactions and can be used to identify potential target genes for therapeutic applications in IVD degeneration.