Identification and validation of aging-related genes in IgA nephropathy

AbstractIgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. Aging is a major risk factor for progression of IgAN to end stage renal disease. The purpose of this study was to identify and verify aging-related genes associated with IgAN through bioinformatics analysis. Microarray datasets of GSE93798 and GSE37460 were downloaded from the Gene Expression Omnibus (GEO) database. The aging-related DEGs (AR-DEGs) associated IgAN was analyzed by R programming software, and then genome ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed. The PPI network of AR-DEGs was then contructed, and hub genes were ranked using five methods of the cytoHubba plugin in Cytoscape software. CIBERSORT algorithm was used to evaluate the infiltrating immune cells and their relationship with hub genes. Next, Nephroseq V5 online platform was used to verify and analyze the mRNA expression patterns of hub genes in IgAN patients and normal controls.A total of 372 DEGs were identified, of which the expression of 158 were upregulated and 214 were downregulated. GO and KEGG enrichment pathway analysis mainly focused on regulation of macrophage derived foam cell differentiation, PI3K-Akt signaling pathway. Based on the results of PPI network analysis, the eight hub genes were identified, includingAGT,ALB,CD36,EGF,KDR,LPL,MYC,PPARGC1A. Immunoinfiltration analysis indicated thatCD36were closely related to immune cell infiltration. Furthermore, the expression levels of these hub genes were validated using the Nephroseq V5 online platform. Further clinical sample studies confirmed thatCD36was highly expressed in renal tissues of IgAN patients. These findings provide new insights into potential aging-related genes associated with IgAN, which may better contribute to understanding the pathogenesis of IgAN.CD36may have diagnostic value for aging-related IgAN.