CXCL1 as a potential therapeutic target for diabetic nephropathy
10.3760/cma.j.cn311282-20230406-00154
- VernacularTitle:以CXCL1为关键靶点的糖尿病肾病差异基因分析及潜在药物预测
- Author:
Xin HU
1
;
Lizhuo WANG
;
Yao ZHANG
;
Wenjun PEI
;
Jinhan CHENG
;
Chaoqun XIONG
;
Yue QIAN
;
Qiuheng ZHANG
;
Xu WU
;
Ying YANG
;
Jialin GAO
Author Information
1. 皖南医学院弋矶山医院内分泌科，芜湖 241000
- Keywords:
Diabetic nephropathy;
Microprotein array;
Protein interaction network;
Drug screening;
CXCL1;
GO enrichment analysis;
KEGG enrichment analysis
- From:
Chinese Journal of Endocrinology and Metabolism
2023;39(12):1056-1066
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To screen highly expressed inflammatory factors in diabetic nephropathy models using protein microarray, analyze differential genes and their regulatory networks, and predict potential therapeutic small molecular compounds.Methods:The inflammatory factor microarray was used to screen the inflammatory factors with the same tendency in the cell model and animal model of diabetic nephropathy. The differential genes screened by R language were enriched and analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG). STRING builds a protein interaction network online, Cytoscape software analyzes the core subnetwork, and Connectivity Map searches for and predicts small molecule compounds.Results:Diabetic nephropathy model was established using 16-week-old db/db mice and mesangial cells stimulated with high glucose, and the expression of C-X-C motif chemokine ligand 1(CXCL1) was elevated in both models. Multiple GEO datasets indicated a strong association between the high expression of CXCL1 and diabetic nephropathy. Specifically, GSE30122 showed an upregulation of 30 genes and a downregulation of 23 genes. GO enrichment analysis focused on biological processes such as humoral immunity and lipopolysaccharide response; While KEGG enrichment was mainly in pertussis and coagulation cascade pathways. CytoHubba identified 10 hub genes, such as ALB, LUM, and CXCL1. In addition, 10 small molecule compounds were predicted as potential therapeutic drugs using Connectivity Map.Conclusions:CXCL1 may serve as a key gene in the occurrence and development of diabetic nephropathy. ALB, LUM, CXCL1, MMP7, TGFBI, CCL2, S100A4, SOX9, VCAN, and CLU may participate in the regulatory network centered around CXCL1. There are 10 small molecular compounds demenestrating the potential to be therapeutic agents.
