Xin yixue (Jun 2023)

CCL20 regulates inflammatory progression in diabetic nephropathy through IL-17 signaling pathway

  • Dong Lan, Zhao Sheng, Li Wenchuan, Li Yuejiao, Lian Rong, He Feng

DOI
https://doi.org/10.3969/j.issn.0253-9802.2023.06.006
Journal volume & issue
Vol. 54, no. 6
pp. 403 – 409

Abstract

Read online

Objective To identify key genes in the peripheral blood of diabetic nephropathy （DN） patients based on weighted gene co-expression network analysis （WGCNA），aiming to explore the pathogenesis of DN and provide new insights into the incidence and development of DN. Methods In this study，the dataset GSE142153 was downloaded from the Gene Expression Omnibus （GEO） database to screen the differentially expressed genes （DEGs）. Then，Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis was employed to investigate the molecular biological processes of these DEGs. Key modules and hub genes were identified by constructing WGCNA. The validation dataset GSE65561 was applied to analyze the receiver operating characteristic （ROC） curve to validate the potential clinical diagnostic value of hub genes. Subsequently，RT-qPCR was adopted to detect the relative expression levels of hub genes in the peripheral blood of DN patients. Results There were 23 patients with DN and 10 healthy controls in the dataset GSE142153. According to the screening criteria，there were 181 DEGs in the DN group，of which 106 DEGs were up-regulated and 75 were down-regulated. KEGG enrichment analysis mainly showed the activation of inflammatory pathways，such as interleukin （IL）-17，nuclear factor-κB （NF-κB），and JAK-STAT signaling pathways. Sixteen modules were identified by WGCNA and the turquoise module was considered to have the most clinical significance for DN. The genes in the turquoise module were selected to intersect with DEGs and IL-17 signaling pathway-related genes to obtain 5 hub genes including Chemokine （C-C motif） ligand 20 （CCL20），IL-1B，CXCL1，matrix metalloproteinase-9 （MMP-9） and Fos-like antigen 1 （FOSL1）. The results of RT-qPCR of the peripheral blood of DN patients were consistent with the bioinformatic analysis. Conclusion The hub genes，such as CCL20，may play a key role in promoting the inflammatory progression of DN through regulating the IL-17 signaling pathway，which contribute to identifying potential biomarkers and therapeutic targets for DN.

Keywords