肾纤维化中心基因的鉴定

Identification of Hub genes in renal fibrosis

目的 肾纤维化(renal fibrosis, RF)是指引起肾脏细胞外基质异常沉积并取代正常肾脏结构的病理生理变化,是慢性肾脏病(chronic kidney disease,CKD)发展到终末期肾病(end stage renal disease,ESRD)的唯一途径。RF的防治是遏制CKD进展的关键,也是肾脏疾病研究的热点和难点。因此,确定与RF相关的中心基因对于开发防治RF的新策略至关重要。方法 分析了两个数据库(GSE35257和GSE121190)肾脏组织的基因表达特征,并利用GEO2R工具获得差异表达基因(differential expression genes,DEGs)。然后,使用DAVID数据库进行GO分析以及KEGG富集分析。随后,我们使用STRING数据库并构建了PPI网络,最后使用Cytoscape软件的cytoHubba插件来选择中心基因。结果 从GSE35257数据库中筛选了930个DEGs,包括504个上调DEGs和426个下调DEG;从GSE121190数据库中过滤了2053个DEGs,包括898个上调DEGs和1155个下调DEGs。功能富集分析表明,DEGs涉及许多功能和表达途径,如细胞外泌体、对药物反应、NAD或NADP作为受体、核系统、发育、蛋白激酶结合等途径。它由97个节点(蛋白质)和404个PPI边缘(相互作用)构建的PPI网络中得到证明。最后得到GAPDH、CCND1、ACTA2、MTOR、ABL1、ANK3、CXCL12、PRRX1、CTSB、MAP2K7在内的十个基因被确定为RF相关的中心基因的新候选者。结论 研究的结果提示RF的发病机制和潜在的新治疗靶点提供了全面的见解。

Objective Renal fibrosis(RF)is a pathophysiological change leading to abnormal deposition of extracellular matrix in kidney and replacement of normal renal structure.It is the sole pathway for a rapid progression of chronic kidney disease(CKD)into end-stage renal disease(ESRD).Preventing and treating RF are vital for arresting the progression of CKD.It has been a hot spot and a difficult point of kidney disease researches.Therefore identifying key genes associated with RF is crucial for developing new strategies for RF.Methods The gene expression characteristics of kidney tissues were retrieved from two databases(GSE35257&GSE121190)and geo2R was employed for obtaining the differentially expressed genes(DEG).Then Database for Annotation,Visualization and Integrated Discovery(DAVID)for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)were utilized.Subsequently the STRING database was employed for constructing a protein-protein-interactions(PPI)network and cytoHubba plug-ins of Cytoscape were utilized for selecting hub genes.Results A total of 930 DEGs were harvested from GSE35257 database,including 504 up-regulated DEGs and 426 down-regulated DEGs.And 2053 DEGs were filtered from GSE121190 database,including 898 up-regulated DEGs and 1155 down-regulated DEGs.Functional enrichment analysis revealed that DEGs involved many functional and expression pathways,such as exosome,drug response,NAD/NADP as receptor,nuclear system,development and protein kinase binding.PPI network was composed of 97 nodes(proteins)and 404 PPI edges(interactions).Finally,ten genes including GAPDH,CCND1,ACTA2,MTOR,ABL1,ANK3,CXCL12,PRRX1,CTSB and MAP2K7 were identified as new candidates for rF-related key genes.Conclusions The results of this study provide comprehensive insights into the pathogenesis of RF and designing potential new therapeutic targets.