Jinlian Shu, He Li, Hairong Li

Department of Nephrology, The Second People’s Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, Anhui, People’s Republic of China

Correspondence: Jinlian Shu, Email 1210497702@qq.com

Background: IgA 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.
Methods: Microarray datasets of GSE93798 and GSE37460 were downloaded from the Gene Expression Omnibus (GEO) database. The aging-related DEGs (AR-DEGs) associated with IgAN were analyzed using R programming software, and then Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed. The PPI network of AR-DEGs was then constructed, and hub genes were ranked using five methods of the cytoHubba plugin in Cytoscape software. CIBERSORT algorithm was used to evaluate immune infiltration and its 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.
Results: A total of  372 differentially expressed genes (DEGs) were identified, of which 158 were upregulated and 214 were downregulated. GO and KEGG enrichment analyses mainly focused on regulation of macrophage-derived foam cell differentiation and PI3K-Akt signaling pathway. Based on the results of PPI network analysis, eight hub genes were identified, including AGT, ALB, CD36, EGF, KDR, LPL, MYC, and PPARGC1A. Immune infiltration analysis indicated that CD36 was closely related to immune cell infiltration. Furthermore, the expression levels of these hub genes were validated using the Nephroseq V5 online platform. Further clinical samples confirmed that CD36 was highly expressed in renal tissues of IgAN patients.
Conclusion: These findings provide new insights into potential aging-related genes associated with IgAN, which may contribute to better understanding the pathogenesis of IgAN. CD36 may have diagnostic value for aging-related IgAN.

Keywords: IgA nephropathy, aging, bioinformatics analysis, hub genes, differentially expressed genes