摘要目的:通过蛋白微阵列筛选糖尿病肾病模型中高表达的炎症因子,利用生物信息学分析差异性基因及其调控网络,并预测可能具有治疗作用的小分子化合物。方法:利用炎症因子芯片筛选糖尿病肾病细胞模型和动物模型中具有相同趋势的炎症因子。通过基因本体论(Gene Ontology, GO)和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes, KEGG)富集分析R语言所筛选的差异性基因。STRING在线构建蛋白互作网络,Cytoscape软件解析核心子网络,Connectivity Map寻找预测小分子化合物。结果:16周db/db小鼠和高糖刺激的系膜细胞被确定为糖尿病肾病的模型,其中趋化因子(C-X-C基序)配体1(C-X-C motif chemokine ligand 1, CXCL1)的表达在两模型中均有升高。多个GEO数据芯片均显示CXCL1的高表达与糖尿病肾病有明显关联。其中GSE30122包括30个基因的上调和23个的下调。GO富集分析集中在体液免疫和脂多糖反应等生物过程;而KEGG富集主要在百日咳和凝血级联通路。CytoHubba识别了10个中枢基因,例如ALB、LUM和CXCL1等。此外,使用Connectivity Map预测了10种小分子化合物作为潜在的治疗药物。结论:CXCL1可能是糖尿病肾病发生发展的关键基因,ALB、LUM、CXCL1、MMP7、TGFBI、CCL2、S100A4、SOX9、VCAN和CLU可能参与以CXCL1为中心的调控网络,有10种小分子化合物可能作为潜在的治疗药物。
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abstractsObjective: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.
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