BackgroundIgA nephropathy (IgAN), which has been reported as the most prevalent glomerulonephritis globally, is the major contributor to end-stage renal illness. This bioinformatics study aimed to explore glomeruli-tubulointerstitial crosstalk genes and dysregulated pathways relating to the pathogenesis of IgAN. MethodsThe microarray datasets from the Gene Expression Omnibus (GEO) database were searched. Weighted gene co-expression network analysis (WGCNA) and differentially expressed genes

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... s) of both glomeruli and tubulointerstitial were conducted individually. The co-expression gene modules of tubulointerstitial and glomeruli were compared via gene function enrichment analysis. Subsequently, the crosstalk co-expression network was constructed via the STRING database and key genes were mined from the crosstalk network. Results583 DEGs and eight modules were identified in glomeruli samples, while 272 DEGs and four modules were in tubulointerstitial samples. There were 119 overlapping DEGs of the two groups. Among the distinctive modules, four modules in glomeruli and one module in tubulointerstitial were positively associated with IgAN. While four modules in glomeruli and two modules in tubulointerstitial were negatively associated with IgAN. The top ten key genes screened by CytoHubba were ITGAM, ALB, TYROBP, ITGB2, CYBB, HCK, CSF1R, LAPTM5, FN1and CTSS. The above genes were all validated using another two datasets, and all of the key genes demonstrated possible diagnostic significance. Conclusionshe crosstalk genes confirmed in this study may provide novel insight into the pathogenesis of IgAN. Immune-related pathways are associated with both glomerular and tubulointerstitial injuries in IgAN. The glomerulotubular crosstalk might perform a role in the pathogenesis of IgAN.