Abstract
Recurrent aphthous stomatitis (RAS) represents the most common chronic oral diseases with the prevalence ranges from 5% to 25% for different populations. Its pathogenesis remains poorly understood, which limits the development of effective drugs and treatment methods. In this study, we conducted systemic bioinformatics analysis of gene expression profiles from the Gene Expression Omnibus (GEO) to identify potential drug targets for RAS. We firstly downloaded the gene microarray datasets with the accession number of GSE37265 from GEO and performed robust multi-array (RMA) normalization with affy R programming package. Secondly, differential expression genes (DEGs) in RAS samples compared with control samples were identified based on limma package. Enriched gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of DEGs were obtained through the Database for Annotation, Visualization and Integrated Discovery (DAVID). Finally, protein-protein interaction (PPI) network was constructed based on the combination of HPRD and BioGrid databases. What’s more, we identified modules of PPI network through MCODE plugin of Cytoscape for the purpose of screening of valuable targets. As a result, 915 genes were found to be significantly differential expression in RAS samples and biological processes related to immune and inflammatory response were significantly enriched in those genes. Network and module analysis identified FBXO6, ITGA4, VCAM1 and etc as valuable therapeutic targets for RAS. Finally, FBXO6, ITGA4, and VCAM1 were further confirmed by real time RT-PCR and western blot. This study should be helpful for the research and treatment of RAS.
Highlights
Despite the rapid development of anticatarrhals and treatment methods, recurrent aphthous stomatitis (RAS) still represents the most common chronic oral disease, which suffered from a long-term painful and characterized by a yellowish ulcer and with an erythematous halo that heals spontaneously [1,2,3]
Based on the criteria of FDR < 0.05 and fold change > 2, we identified a total of 915 differential expression genes (DEGs) in Recurrent aphthous stomatitis (RAS) samples compared with adjacent nonulcer tissue
A total of 215 gene ontology (GO) terms and 24 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were found to be significantly enriched in the DEGs
Summary
Despite the rapid development of anticatarrhals and treatment methods, recurrent aphthous stomatitis (RAS) still represents the most common chronic oral disease, which suffered from a long-term painful and characterized by a yellowish ulcer and with an erythematous halo that heals spontaneously [1,2,3]. The prevalence of RAS could variy from 5% to 25% for people with different diet habits and come to the highest for people between 10-40 years of age [4]. Several inducing factors, such as work-rest schedule, stress, smoking, stress, and etc are summaried, and these factors may joint to influence the pathological process. The progress of molecular has accelerate the emergence of novel drugs and therapeutic methods for the pain relase and reduction of RAS recurrence frequency, while, there is still no effective methods for its healing
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