人类巨细胞病毒感染对淋巴系祖细胞增殖过程中Hoxc4及Hoxc6基因表达的影响  

Effect of Human Cytomegalovirus Infection on the Expression of Hoxc4 and Hoxc6 genes in the Proliferation of Lymphocytic Progenitor Cells

作　　者：冯静乔[1,2] 刘文君[1] 陈红英[1] 郭渠莲[1] 陈艾[1] 陈书琴[1] 

机构地区：[1]四川省泸州医学院附属医院儿科,四川泸州646000 [2]广东省汕头市妇幼保健院儿科

出　　处：《中国实验血液学杂志》2009年第1期141-145,共5页Journal of Experimental Hematology

基　　金：四川省教育厅重点科研基金,编号2004A058

摘　　要：本研究探讨人类脐血造血干细胞(HSC)向淋巴系祖细胞(CFU-TL)分化过程中hoxc4、hoxc6基因表达的情况,并且用人类巨细胞病毒(HCMV)和/或全反式维甲酸(ATRA)进行干扰,在基因水平探讨HCMV感染导致脐血CFU-TL损伤的机制。采用体外定向培养CFU-TL,经MTT法检测后,应用荧光定量RT-PCR技术检测经人HCMV和/或ATRA处理的人脐血CFU-TL中hoxc4、hoxc6基因的mRNA表达水平。HCMV-AD169滴度为106蚀斑形成单位(PFU)/ml,按0.1ml105PFU/ml接种培养体系。结果表明:正常对照组、病毒处理组、维甲酸处理组hoxc4、hoxc6基因均在增殖分化的第3天少量表达,第7天表达最强烈(p<0.05),第12天表达明显下降。各组中hoxc4基因表达量高于hoxc6组(p<0.05)。与正常对照组比较,维甲酸组(6×10-8mol/L)的hoxc4、hoxc6基因表达上调(p<0.05),而病毒处理组hoxc4、hoxc6基因表达下调(p<0.05)。结论:hoxc4与hoxc6基因在脐血CFU-TL中各组呈现规律的表达,提示hoxc4、hoxc6均与淋巴系造血有密切的相关性。HCMV能使hoxc4、hoxc6基因表达下调,提示HCMV致造血细胞损害可能与hoxc4、hoxc6基因表达异常有关。ATRA能显著上调hoxc4、hoxc6基因的表达。The objective of this study was to observe the expression of hoxc4 and hoxc6 genes in the process of differentiation of hematopoietic stem cell （HSC） to colony forming unit-T Lymphocyte （CFU-TL） in vitro, and to explore the possible mechanism of HCMV-induced maldevelopment of human cord blood CFU-TL on genetic level through effecting the differentiation progress by human cytomegalovirus （HCMV） with and/or all-trans retinoic acid （ATRA）, Normal CFU-TL culture was used as blank control. After detection with MTT, mRNA expression levels in the human cord blood CFU-TL hoxc4 and hoxc6 genes following HCMV infection and ATRA treatment were detected by fluorogenic quantitative reserve transcription polymerize chain reaction （FQ-RT-PCR） method. HCMV of 106 plaque formation unit （PFU）/ml was diluted to 0.1 ml 105 PFU/rnl and added into the infected group. The results showed that the expression of hoxc4 and hoxc6 genes in the differentiation process increased slightly on day 3, and were up to the most on day 7 （p 〈 0.05）, while became lower on day 12 respectively in normal group, HCMV group and ATRA group. Compared with the expression of hoxc6, the expression of hoxc4 was obviously higher in each group（p 〈 0.05 ）. Compared with the expression of hoxc4 and hoxc6 genes in normal group, the expressions of hoxc4 and hoxc6 in ATRA group were up-regulated remarkably （p 〈 0.05）, while the expressions of hoxc4 and hoxc6 in group HCMV were down- regulated （p 〈 0.05 ）. It is concluded that the regular expression of hoxc4 and hoxc6 genes mRNA appeared in each group. A positive co-relationship exits between hoxc4/hoxc6 genes and lymphocytic progenitor hematopoiesis. Compared with the expression of hoxc6 gene, the expression of hoxc4 gene is obviously higher in each group. HCMV can down-regulate the expression of hoxc4 and hoxc6 genes and lead to suppression effect on cell morphology, which confirms that the normal hematopoietic lineage determination and maturation rely on the stable and c

关 键 词：巨细胞病毒 淋巴系祖细胞 全反式维甲酸 HOX基因 hoxc4基因 hoxc6基因 

分 类 号：R373.11[医药卫生—病原生物学] R329.28[医药卫生—基础医学]