An Integrative Analysis to Identify Potential Angiogenesis Key Genes and Their Mechanism of Action in the Pathogenesis of Idiopathic Pulmonary Fibrosis

Background: Idiopathic pulmonary fibrosis (IPF) is a lung condition marked by microscopic honeycombing, subepithelial fibroblastic foci, and subpleural fibrosis, which is typically deadly, irreversible, and progressive. Angiogenesis is crucial to the development of pulmonary fibrosis. Nevertheless, the underlying molecular events involved remain unclear. The aim of this study was to identify specific central gene expression in pulmonary fibrosis and its underlying mechanism of action. Methods: GSE53845 dataset of pulmonary fibrosis patients were obtained from Gene Expression Omnibus (GEO) database to screen the differentially expressed genes (DEGs) and conducted principal component analysis. Differentially expressed ARGs (DE-ARGs) were obtained, by cross-analysis of angiogenesis-related genes (ARGs) and DEGs, downloaded from GeneCards. DE-ARGs were enriched using the R package clusterProfiler. Geneset variation analysis (GSVA) and gene set enrichment analysis (GSEA) were employed, to analyse the characteristics of related common pathways and the biological processes of DE-ARGs. In addition, protein-protein interaction (PPI) molecular regulatory interaction networks were created and hub DE-ARGs were screened. The correlation between IPF and immune cell infiltration was checked for, using the CIBERSORT algorithm. Quantitative Reverse Transcription Polymerase Chain Reaction (RT-qPCR) was employed, to examine hub DE-ARG expression in IPF rat tissues. Results: A total of 117 DE-ARGs were obtained, and these genes were primarily involved in biological activities including leukocyte migration, cell chemotaxis, and angiogenesis. In addition, eight hub DE-ARGs were identifie: CCR7, CD24, MDK, CXCL12, IL1R2, CXCL14, CCL19, and IL13RA2. Furthermore, miR-374a-5p was significantly associated with CD24, CXCL14, IL13RA2 and CXCL12 central genes. Immune infiltration analysis showed a significant rise in the number of infiltrating B cells and CD8+ T cells in patients with IPF. Conclusions: Hub DE-ARGs may contribute to the angiogenic process of pulmonary fibrosis, providing potential targets for treating IPF, which is influenced by changes in the abundance of immune cells.