Identification of differentially expressed genes triggered by aberrant methylation in idiopathic pulmonary fibrosis using integrated bioinformatic analysis
Abstract Background Idiopathic pulmonary fibrosis (IPF) is a relentlessly progressive and fatal fibrotic lung disease all over the world, and specific pathogenesis is still not well understood. DNA methylation is an essential epigenetic mechanism, which likely contributes to the progress of IPF. The purpose of this study is to identify aberrantly methylated differentially expressed genes (DEGs) in IPF and to explore the underlying mechanisms of IPF by using integrated bioinformatics analysis.Methods Gene expression profiles and gene methylation profiles were downloaded and analyzed to identify the aberrantly methylated‐differentially expressed genes. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Search Tool for the Retrieval of Interacting Genes Database (STRING), and Gene set enrichment analysis (GSEA) were used to evaluate the function of DEGs. RT-PCR was used to verify the mRNA levels of DEGs in mice with pulmonary fibrosis.Results By analyzing the differentially expressed genes of the three IPF expression profiles, and taking the intersection, we got 143 co-upregulated genes and 104 co-downregulated genes; GO and KEGG pathway analysis of the DEGs suggested these genes involved in the extracellular matrix organization, multicellular organismal homeostasis. Combining the sequencing data of two IPF methylation chips, we have identified genes that may be regulated by methylation in IPF. Finally, we obtained the mRNA expression of DEGs using a mouse model of pulmonary fibrosis.Conclusions Through integrated analysis and experimental verification, we found a series of biomarkers that were regulated by methylation should be potential therapeutic targets for IPF.