高糖诱导阴茎海绵体内皮细胞损伤关键基因的筛选和生物信息学分析

Screening of key genes related to high glucose-induced penile cavernous chondrocyte damage using bioinformatics analysis

目的通过生物信息学分析,筛选高糖诱导的阴茎海绵体内皮细胞损伤关键差异基因,预测糖尿病性勃起功能障碍(DED)的潜在治疗靶点。方法在GEO(Gene Eexpression Omnibus)数据库中下载高糖环境下阴茎海绵体内皮细胞损伤的芯片表达谱(GSE146078),利用GPL17021平台初步筛选正常对照组和高糖致内皮细胞损伤组的差异基因,采用STRING进行蛋白质与蛋白质相互作用网络验证,利用Cytoscape的Hub插件分析Hub核心基因,使用R软件对差异基因进行GO功能注释,使用DAVID数据库KEGG通路富集分析。结果共筛选到367个差异表达基因,其中包含有150个上调基因,217个下调基因。核心差异基因包括上调表达基因Ccl19、Cxcl1、IL-6、Zscan4家族、GSTA家族、CYP2D家族及Saa家族成员和下调表达基因Cxcl12、Sox9。其中血清淀粉样蛋白A(Serum amyloid A,Saa)家族成员Saa1、Saa2、Saa3均显著上调表达,并与Lcn2、Orm2、Pon1及Apoa1等多个载脂蛋白或脂相关蛋白有关联。GO分析发现Saa家族主要与胆固醇代谢、脂解反应,脂蛋白代谢等过程相关。KEGG分析发现Saa家族主要参与PPAR信号通路以及胆固醇代谢。结论Saa家族成员在高糖处理的小鼠阴茎海绵体内皮细胞中呈高表达状态,并与脂蛋白代谢等过程相关。因此我们推测Saa家族可能通过载脂或脂相关蛋白参与DED的发生和发展过程,但具体作用有待进一步的功能验证。

Objective To screen the key differential genes of high glucose-induced penile cavernous endothelial cell damage using bioinformatics analysis,and predict potential therapeutic targets for diabetic erectile dysfunction(DED).Methods Microarray expression profile(GSE146078)of high glucose-cuasedpenile cavernous endothelial cells damage was downloaded from GEO(Gene Expression Omnibus)database.The GPL17021 platform was used to preliminarily screen the differential genes between the control group and the high glucose-induced endothelial cell injury group.STRING was used to verify the protein-protein interaction network,the core genes were analyzed by Cytoscape.GO function annotation of the differential genes was performed by using R software,and the KEGG pathway enrichment analysis was performed by using David database.Results A total of 367 differentially expressed genes were screened,including 150 up-regulated genes and217 down-regulated genes.Core differential genes includedup-regulated genes Ccl19,Cxcl1,IL-6,Zscan4 family,GSTA family,CYP2 D family and Saa family,as well as down-regulated genes Cxcl12,Sox9.Serum amyloid A(serum amyloid A,Saa)family members Saa1,Saa2,and Saa3 were significantly up-regulated,and associated with multiple apolipoproteins or lipo-related proteins such as Lcn2,Orm2,Pon1 and Apoa1.GO analysis found that the Saa family was related to diabetes metabolism,lipolysis reaction,lipoprotein metabolism and other processes.KEGG analysis showed that the Saa family was involved in the PPAR signaling pathway and metabolism.Conclusion SAA family members are highly expressed in the mouse penile cavernous endothelial cells with high glucose,and related to lipoprotein metabolism and other processes.Therefore,we speculate that the Saa family may be involved in the occurrence and development of DED through apolipoproteins or lipo-related proteins,but the specific role needs to be further investigated.