关键词:

糖尿病肾病, 生物信息学, CCR2, 炎症反应

Abstract:

Objective To analyze and explore the differential gene expression and pathogenesis of early diabetic nephropathy with bioinformatics analysis，and to explore the pathogenesis of diabetic nephropathy and provide new molecular therapeutic targets for it. Methods In this study，the data set GSE142025 was obtained from the GEO database for bioinformatics analysis，and the differentially expressed genes were screened in the early diabetic nephropathy group（eDN group）when compared with those in normal control group（NC group）. The enrichment pathways of differentially expressed genes were analyzed by GSEA，and HUB genes were identified by protein interaction network（PPI）analysis. The relative expression levels of target genes in kidney tissue were detected by immunohistochemistry and RT ⁃qPCR. Results A total of 1，859 differentially expressed genes were screened using P < 0.05 and |log2FC| > 1 as the criteria in the eDN group. Among them，the expression of 1，063 was up ⁃ regulated and that of 796 down ⁃ regulated. The KEGG pathway enrichment of differential genes in GSEA showed that the eDN group weresignificantly up ⁃ regulated in the“JAK ⁃ STAT pathway”，“Cytokine receptor pathway”，“Chemokine signaling pathway”，“Cell adhesion molecule pathway”，and“Extracellular matrix receptor interaction”. As a HUB gene，the expression of CCR2 was significantly up⁃regulated in eDN；immunohistochemistry and RT⁃qPCR showed that the relative expression of CCR2 in eDN group was significantly higher than that in NC group（all P < 0.05）. Conclusion KEGG analysis of functional enrichment mainly shows that the inflammatory pathway is activated，and the expression of CCR2 is significantly up ⁃ regulated in eDN kidney tissue，suggesting that it may play an important role in the occurrence and development of eDN.

Key words:

diabetic nephropathy, bioinformatics, CCR2, inflammation