Bioinformatics analysis of fibroblasts exposed to TGF-β at the early proliferation phase of wound repair

The aim of the current study was to identify gene signatures during the early proliferation stage of wound repair and the effect of TGF-β on fibroblasts and reveal their potential mechanisms. The gene expression profiles of GSE79621 and GSE27165 were obtained from GEO database. Differentially expressed genes (DEGs) were identified using Morpheus and co-expressed DEGs were selected using Venn Diagram. Gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of DEGs were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) online tool. Protein-protein interaction (PPI) networks of the DEGs were constructed using Cytoscape software. PPI interaction network was divided into subnetworks using the MCODE algorithm and the function of the top one module was analyzed using DAVID. The results revealed that upregulated DEGs were significantly enriched in biological process, including the Arp2/3 complex-mediated actin nucleation, positive regulation of hyaluronan cable assembly, purine nucleobase biosynthetic process, de novo inosine monophosphate biosynthetic process, positive regulation of epithelial cell proliferation, whereas the downregulated DEGs were enriched in the regulation of blood pressure, negative regulation of cell proliferation, ossification, negative regulation of gene expression and type I interferon signaling pathway. KEGG pathway analysis showed that the upregulated DEGs were enriched in shigellosis, pathogenic Escherichia coli infection, the mitogen-activated protein kinase signaling pathway, Ras signaling pathway and bacterial invasion of epithelial cells. The downregulated DEGs were enriched in systemic lupus erythematosus, lysosome, arachidonic acid metabolism, thyroid cancer and allograft rejection. The top 10 hub genes were identified from the PPI network. The top module analysis revealed that the included genes were involved in ion channel, neuroactive ligand-receptor interaction pathway, purine metabolism and intestinal immune network for IgA production pathway. The functional analysis revealed that TGF-β may promote fibroblast migration and proliferation and defend against microorganisms at the early proliferation stage of wound repair. Furthermore, these results may provide references for chronic wound repair.