Xin yixue (Aug 2022)
IRF4 regulates inflammation progression in diabetic nephropathy through JAK/STAT signaling pathway
Abstract
Objective To screen and analyze the differentially-expressed genes （DEGs） of diabetic nephropathy （DN） by bioinformatics methods, aiming to explore the mechanism of IRF4 in DN, and to find potential molecular targets of DN. Methods The GSE142025 dataset was downloaded from the GEO database, including 9 cases in normal control group and 21 cases in advanced DN（aDN） group, and the DEGs were screened. The GSEA enrichment revealed the molecular biological process of the DEGs. Protein-protein interaction networks of DEG were visualized using String and Cytoscape software. The relative expression levels of major DEGs in six DN renal tissues （DN group） and six normal renal tissues after tumor resection （NC group） were verified using RT-qPCR, PAS and SP staining. Results GEO data analysis revealed 1213 differentially-expressed mRNA, of which 684 were up-regulated and 529 were down-regulated. The GSEA and KEGG pathway enrichment of DEGs showed that the DEGs in the DN group were significantly enriched in the JAK/STAT signaling pathway, chemokine signaling pathway, Fcγreceptor-mediated phagocytosis of macrophages signaling pathway, leukocyte transendothelial migration signaling pathway and T cell receptor signaling pathway. The relative expression levels of IRF4, signal lymphocyte activating molecule 6 and IL-2 receptor α subunit mRNA in the DN group were significantly higher compared with those in the NC group （all P < 0.001）. The PAS and SP staining results were consistent with those of RT-qPCR. Conclusion The GSEA enrichment pathways show that the inflammatory pathway is significantly active, and the expression of IRF4 as a hub gene is significantly up-regulated in the DN tissues, which may be involved in the highly-active inflammatory pathway and promote the progression of inflammation in DN.
Keywords
