狼疮性肾炎患者肾组织差异表达基因筛选及功能分析

Screening and functional analysis of differentially expressed genes in renal tissues of patients with lupus nephritis

目的筛选狼疮性肾炎(LN)患者肾组织中差异表达基因(DEGs)并对其进行功能分析。方法GSE32591和GSE112943数据集分别包括LN肾小管间质、LN肾小球、LN肾组织及其各自的正常对照组织的转录组数据;GSE81622包含LN患者及健康对照者外周血单个核细胞(PBMC)转录组数据。利用GEO2R在线分析工具筛选DEGs。利用DAVID对筛选的DEGs进行基因本体(GO)和京都基因与基因组百科全书(KEGG)通路富集分析。利用STRING数据库进行蛋白互作网络(PPI)分析,并筛选核心DEGs。分析LN肾组织中核心DEGs在LN患者PBMC中的表达变化情况。结果LN肾组织中共筛选出37个表达上调基因和8个表达下调基因。GO分析显示,DEGs主要参与和病毒防御相关的生物过程,如病毒的响应、Ⅰ型干扰素信号通路等,分子功能包括RNA结合、GTP结合及解旋酶活性等。KEGG通路分析显示DEGs主要参与病毒感染相关通路。PPI分析筛选出12个核心DEGs:EGR1、FOSB、IFI27、IFI6、IFIT2、IFIT3、IFITM1、IFITM3、MX1、MX2、OAS1、XAF1,其中除EGR1表达下调外(P<0.01),其余DEGs均表达升高(P<0.01)。然而,在LN的PBMC中,EGR1表达上调(P<0.01),FOSB和IFITM1的表达变化差异无统计学意义(P>0.05),其他9个核心DEGs表达上调(P<0.01),与在LN肾组织中变化一致。结论LN患者肾组织中关键DEGs主要与干扰素信号通路相关。

Objective To screen differentially expressed genes(DEGs)in renal tissues of patients with lupus nephritis(LN)and to analyze their functions.Methods The GSE32591 and GSE112943 datasets included the transcriptome data of LN tubulointerstitium,LN glomerulus,LN renal tissues and their normal control tissues,respectively.GSE81622 included the transcriptome data of peripheral blood mononuclear cells(PBMC)from LN patients and healthy controls.DEGs were screened using online analysis tool GEO2R.DAVID was used to perform Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis of the selected DEGs.Protein-protein interaction network(PPI)analysis was performed using STRING database,and the core DEGs were screened.The expression changes of core DEGs in renal tissues of LN patients in PBMC were analyzed.Results A total of 37 up-regulated genes and 8 down-regulated genes were screened in LN renal tissues.GO analysis showed that DEGs were mainly involved in biological processes related to virus defense,such as virus response and typeⅠinterferon signaling pathway,and their molecular functions included RNA binding,GTP binding and helicase activity.KEGG pathway analysis showed that DEGs were mainly involved in viral infection-related pathways.PPI analysis identified 12 core DEGs:EGR1,FOSB,IFI27,IFI6,IFIT2,IFIT3,IFITM1,IFITM3,MX1,MX2,OAS1,XAF1,among which the expression of EGR1 was down-regulated(P<0.01),and the expression of other DEGs was increased(P<0.01).However,the expression of EGR1 was up-regulated in PBMC of LN(P<0.01),and there was no significant difference in the expression of FOSB and IFITM1(P>0.05).The expression of other 9 core DEGs was up-regulated(P<0.01),which was consistent with the changes in LN renal tissue.Conclusion The key DEGs in renal tissue of LN patients are mainly related to interferon signaling pathway.