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Reseacrh On Gene Expression Profiling And Renal Injury Related Gene In Children With Henoch-Schonlein Purpura

Posted on:2013-09-23Degree:MasterType:Thesis
Country:ChinaCandidate:J LiFull Text:PDF
GTID:2234330374473599Subject:Academy of Pediatrics
Abstract/Summary:PDF Full Text Request
Objective:To filter the related genes of Children Henoch-Schonlein purpura developmentand renal injury by The Roche NimbleGen Human gene expression profilesmicroarray technology,to further analyze the pathogenesis of Children Henoch-Schonlein purpura development and renal injury from the molecular level, morecomprehensive and systematic.Methods:To detect the gene expression profiles of the peripheral blood of simpleHenoch-Schonlein purpura group (HSP),Henoch-Schonlein purpura nephritis group(HSPN) and healthy controls (C) by the Roche NimbleGen Human gene expressionprofiles microarray (Contains about45,033genes),respectively. To analyze thedifferential of gene expression profiles between different experimental groups byrelevant biological information.Finally, the part of the differentially expressed geneswere validated by real-time quantitative PCR.Results:1、Simple Henoch-Schonlein group and control group:there are a total of1064differentially expressed genes, of wich225genes in more than two times,38genesmore than2.5times and5genes more than3times; There are146genes upregulatedand79genes downregulated in the differentially expressed genes of more than twotimes. Henoch-Schonlein purpura nephritis group and simple Henoch-Schonleinpurpura group: There are a total of830differentially expressed genes, of wich283genes in more than two times,118genes more than2.5times and51genes morethan3times; There are180genes upregulated and103genes downregulated in thedifferentially expressed genes of more than two times.2、Three differentially expressed genes were randomly selected for validationusing the real-time quantitative PCR, the results and microarray results are consistent.It fully confirmed the reliability of differentially expressed genes results of Human gene expression profiles microarray analysis.3、 The more than2-fold differentially expressed genes between simpleHenoch-Schonlein purpura group and control group were analyzed by the GObiology process analysis and were found that there are A total of119genes whosefunctional classification were crear. These differentially expressed genes mainlyinvolve the related genes of transcription/translation, material synthesis/metabolismprocess and signal transduction/pathway, then the differentiation/growth、immune/inflammatory and apoptosis/anti-apoptosis related genes. But in the more than2-folddifferentially expressed genes between Henoch-Schonlein purpura nephritis groupand simple Henoch-Schonlein purpura group, we discover there are201genes whosefunctional classification were crear. They mainly involve the related genes ofmaterial synthesis/metabolism process, then the transcription/translation immune/inflammatory、signal transduction/pathway、differentiation/growth and mitotic cyclerelated genes.4、The related genes of immune inflammatory/cell adhesion/signal transductionpathway:AIF1,LAMC2,BCAM,CD209,MFAP4,ELMOD3,SCUBE1,ADAM33,RET,CLEC7A, MASP2, TAPS, AOAH, MGST2, PSMA3, SP100, metabolism/apoptosisrelated genes:MUC3B,MUC1,HSD11B1,MTHFS,TNFAIP8,and unknown genesBM88, CEACAM3,etc.were preliminary screened,which may play an important rolein HSP pathogenesis.The immunity inflammation/signal transduction pathwayrelated genes KRT18, GRB10,VEGFB, HSP90AB1, HSPD1,F12,TGFBR2,TGM2,UBE2L6,CTSS,PXDN,GBP2,HLA-DRB1,HLA-DMA,HLA-DPA1,metabolism/differentiation growth/apoptosis related genes SORD, HSPE1,ARG2, HSP90AA2,PRAME, TNFAIP2, MMP19,ZFP36L1,cell adhesion related genes CLDN4andunknown genes CKMT1B etc. were also screened,wich may be closely related withthe occurrence of HSP kidney injury.Conclusion:1、The related genes of Henoch-Schonlein purpura and Henoch-Schonleinpurpura nephritis were screened by the rapid high throughput gene expressionprofiles microarray for the first time.2、The susceptibility genes(AIF1,BCAM,CLEC7A,CD209,AOAH,MAPS2etc.) wich may lead to HSP onset were preliminary screened. Our study further confirmsthe abnormal expression of immune inflammation and cell adhesion-related genesmay play a leading role in HSP pathogenesis,while also founds that some of themetabolism/apoptosis related genes (such as MUC3B,HSD11B1,MTHFS,TNFAIP8,etc.) and unknown genes which may cause HSP occurred.3、The study not only confirms the known genes such as VEGFB and HLA-DRB1which may play an important role in the process of the HSP renal injury, butalso first discovere some of the known genes (such as SORD,ARG2,ZFP36L1,TGM2,KRT18etc.)and unknown genes which had not been reported in HSPNincidence process in the past.4、In-depth study of these genes will help to reveal the molecular mechanism ofallergic Purpura more fully and systematically.
Keywords/Search Tags:Henoch-Schonlein purpura, Henoch-Schonlein purpura nephritis, genechips, gene
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