Identification and validation of glomerulotubular crosstalk genes mediating IgA nephropathy by integrated bioinformatics

Abstract

Background IgA nephropathy (IgAN), which has been reported as the most prevalent glomerulonephritis globally, is the major contributor to end-stage renal diseases. This bioinformatics study aimed to explore glomerulotubular crosstalk genes and dysregulated pathways relating to the pathogenesis of IgAN. Methods The microarray datasets from the Gene Expression Omnibus (GEO) database were searched. Weighted gene co-expression network analysis (WGCNA) and differentially expressed genes (DEGs) of both glomeruli and tubulointerstitium were conducted individually. The co-expression gene modules of glomeruli and tubulointerstitium 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. Finally, key genes were validated using another GEO dataset (GSE99340) containing RNA-seq data of IgAN and lupus nephritis, and their potential diagnostic values were shown using receiver operating characteristic (ROC) analysis. Results Five hundred eighty-three DEGs and eight modules were identified in glomerular samples, while 272 DEGs and four modules were in tubulointerstitial samples. There were 119 overlapping DEGs between the two groups. Among the distinctive modules, four modules in glomeruli and one module in tubulointerstitium were positively associated with IgAN. While four modules in glomeruli and two modules in tubulointerstitium were negatively associated with IgAN. The top ten key genes screened by CytoHubba were ITGAM, ALB, TYROBP, ITGB2, CYBB, HCK, CSF1R, LAPTM5, FN1, and CTSS. Compared with lupus nephritis, there were significant differences in the expression levels of CYBB, CTSS and TYROBP (P < 0.05), while other key genes showed no significant difference. Meanwhile, CYBB, CTSS, and TYROBP demonstrated possible diagnostic significance. Conclusions The 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.

Exploration of potential biomarkers and therapeutic targets for trauma-related acute kidney injury

“… 43 CYBB has been proposed as a primary component of the microbicidal oxidase system of phagocytes. Recent studies have suggested its role in the pathogenesis of immunoglobulin A nephropathy 44 , 45 , though its role in AKI remains unclear. VCAN, a member of the aggrecan/versican proteoglycan family, is involved in cell adhesion, proliferation, migration, and angiogenesis, playing an essential role in tissue morphogenesis and maintenance.…”

Identification of key candidate genes for IgA nephropathy using machine learning and statistics based bioinformatics models

“…According to the GO analysis for BP, the DEGs were statistically significantly associated with inflammatory, camp, and cellular responses to lipopolysaccharide, cytokine-mediated signaling pathway, and neutrophil chemotaxis. Among them, some previous studies found response to inflammatory 10 , 21 , 30 , response to camp 10 , 21 , 22 , 31 , and cellular response to lipopolysaccharide 10 , 21 as highly significant GO terms.…”