摘要
目的 采用生物信息学联合蛋白质组学探究IgA肾病(IgAN)相关差异基因的表达,并筛选相关的靶向中药。方法选取基因表达综合数据库(GEO)的GSE93798和GSE37460数据集,通过R语言筛选IgAN差异表达基因(DEGs),并采用火山图和热图进行DEGs可视化分析。使用韦恩图获取2个数据集的交集DEGs,利用DAVID工具对交集DEGs进行GO和KEGG富集分析,使用STRING筛选交集DEGs的PPI网络,用Cytoscape软件进行拓扑分析以筛选关键基因。收集陕西省中医医院30例IgAN患者和5例微小病变(MCD)患者的尿液样本进行蛋白质组学测定,进一步分析关键基因在IgAN患者尿液中的差异表达,最后利用Coremine Medical预测与IgAN相关的Hub基因的靶向中药。结果 共筛选出52个交集DEGs,包括37个上调和15个下调。GO分析表明交集DEGs主要富集于炎症反应、细胞膜外侧区域等。KEGG富集分析主要包括了细胞外基质受体互作通路、AGE-RAGE信号通路等。利用PPI网络筛选出包括FOS、EGR1、ATF3、FOSB、CD36、POSTN、CYBB、TYROBP、C3AR1、CSF1R、FN1、COL1A1、COL1A2、MMP9、CD68、ALB、CCL2和ITGB2在内的18个关键基因。蛋白质组学分析结果表明FN1、CD36在IgAN患者尿液中的表达均高于MCD患者(P<0.05)。最后,预测了调控17个关键基因的199种中药。结论IgAN差异基因的表达多与机体炎症反应、细胞黏附、信号转导等相关。FN1、CD36在IgAN患者尿液中显著表达,可能成为未来IgAN诊断和治疗的靶点之一。预测得到的中药及其性味、归经与IgAN的病机基本吻合,为未来IgAN的治疗提供新的研究方向和用药参考。
Objective To identify differentially expressed genes(DEGs)associated with IgA nephropathy(IgAN)and explore the un⁃derlying mechanisms and potential targeted Chinese medicines by bioinformatics and proteomics.Methods The GSE93798 and GSE37460 datasets were downloaded from the Gene Expression Omnibus(GEO).Differentially expressed genes(DEGs)between IgAN and healthy controls were identified with R and visualized by volcano plots and heat maps.Overlapping DEGs shared by the two data⁃sets were determined by Venn diagrams,and analyzed using GO and KEGG pathway enrichment analyses with DAVID tools.Protein⁃protein interaction networks were constructed in STRING,and hub genes were selected by topological analysis in Cytoscape.Urine samples from 30 IgAN patients and 5 minimal-change disease(MCD)patients in Shaanxi Provincial Hospital of Traditional Chinese Medicine were collected for proteomic profiling to validate the differential abundance of hub genes in IgAN urine.Finally,Coremine Medical was used to predict traditional Chinese medicines targeting these IgAN-related hub genes.Results A total of 52 overlapping DEGs were identified,including 37 up-regulated and 15 down-regulated genes.GO enrichment indicated that these genes were prima⁃rily involved in inflammatory response and external side of the plasma membrane.KEGG enrichment pathway of DEGs mainly included the ECM⁃receptor interaction pathway,AGE⁃RAGE signaling pathway,etc.Eighteen key genes,including FOS,EGR1,ATF3,FOSB,CD36,POSTN,CYBB,TYROBP,C3AR1,CSF1R,FN1,COL1A1,COL1A2,MMP9,CD68,ALB,CCL2 and ITGB2,were screened out using the PPI network.Proteomic data further showed that urinary FN1 and CD36 levels were significantly higher in IgAN patients than in those with MCD(P<0.05).Finally,199 traditional Chinese medicines were predicted to modulate 17 hub genes.Conclusion The expressions of IgAN differential genes are mostly related to the body′s inflammatory response,cell adhesion, signal transduction, etc. FN1 and CD36 are significantly expressed in the urine of patients with IgAN and may become one of the targets for the diagnosis and treatment of IgAN in the future. The predicted Chinese medicines and their tastes and attributes basically coincide with the pathogenesis of IgAN, providing new research directions and medication references for the treatment of IgAN.
作者
王旭栋
李泽森
何立乾
史健
WANG Xudong;LI Zesen;HE Liqian;SHI Jian(First Clinical Medical College,Shaanxi University of Traditional Chinese Medicine,Xianyang 712046,China;Department of Nephrology,Shaanxi Provincial Hospital of Traditional Chinese Medicine)
出处
《山西医科大学学报》
2025年第8期911-921,共11页
Journal of Shanxi Medical University
基金
陕西省科技厅社会发展领域重点研发项目(2018SF-273)。
