人类巨细胞病毒对粒单系祖细胞分化过程中HOXB6、A5基因的影响

Impact of the expression pattern of HOXB6,HOXA5 homeobox gene on the differentiation of colony for-ming unit-granulocyte-monocyte infected with HCMV

目的探讨人类造血干细胞(HSPC)向粒单系(CFU-GM)增殖过程中HOXB6、A5基因的表达情况,及人类巨细胞病毒(HCMV)对其的影响。方法采用real-timePCR技术测定正常对照组与HCMV组HSPC向CFU-GM增殖过程中HOXB6、A5基因的表达水平。结果①HOXA5基因表达多为阴性,HOXB6基因在增殖过程的第3天开始表达,第7天增高,第12天显著降低(P<0.05)。②相对于正常组,HCMV感染组HOXB6基因表达下调(P<0.05)。结论HOXA5可能不是人类HSPC向CFU-GM增殖分化过程的主控基因;HOXB6是人类HSPC向CFU-GM定向分化的主控基因之一,其表达呈现时间规律性;HCMV干扰的细胞组HOXB6表达下调的同时,其细胞集落生成较正常组差。提示HCMV可能通过调控HOXB6基因表达异常,引起造血干细胞增殖分化异常。

Objectives To investigate the impact of the expression of HOXB6, HOXA5 gene on differentiation of hematopoietic stem-progenitor cell （HSPC） to colony forming unit-granulocyte-macrophage and the influence of human cytomegalovirus （HCMV） on the HSPC differentiation. Methods HCMV-infected group was made by adding 0.1 ml HCMV into cultured cells with concentration of 105 PFU/ml. Normal colony forming unit-granulocyte-monocyte （CFU-GM） culture was used as blank control. The expression of HOXB6, HOXA5 gene of each group was detected with real-time quantitative polymerase chain reaction. Results ①The expression of HOXA5 was almost negative, while the expression of HOXB6 was significantly positive in the normal group. ②The expression of HOXB6 started on the 3rd day of proliferation, and was obviously higher on day 7 and decreased on day 12 （P 〈 0.05）. ③In comparison with the normal group, the expression of HOXB6 was down-regulated by HCMV （P 〈 0.05） . Condusions The HOXA5 gene might not be the key gene in regulating the differentiation and proliferation of HSPC to CFU-GM in vitro. However, HOXB6 gene was one of the key genes playing an important role in directing the differentiation. The expression of HOXB6 gene presented in proper time order. HCMV （0.1 ml 105 PFU/ml） down-regulated the expression of HOXB6 and delivered a suppression effect on the ceil morphology simultaneously, suggesting that HCMV could result in unbalanced proliferation and differentiation of HSPC by errant regulation of the expression of HOXB6 genes.