去整合素基质金属蛋白酶19抑制人正常胎盘来源滋养层细胞的侵润能力

Effect of Adamalysin-19 on Cell Invasiveness in Human Trophoblast Cell Line NPC

去整合素基质金属蛋白酶19(ADAM-19)是新近发现的ADAMs家族成员,在胎盘组织中有较高水平的表达,但其在胎盘发生过程和滋养层细胞侵润中的功能还是未知的.我们以人正常胎盘来源的细胞滋养层细胞(NPC)为体外模型,利用基因转染、RT-PCR、蛋白质印迹、免疫组织化学及细胞侵润分析等手段,证实ADAM-19在人胎盘组织中有特异表达,存在于多种滋养层细胞中;转化生长因子β1(TGF-β1)可以显著上调NPC细胞中ADAM-19的表达,呈现剂量依赖性;过表达hADAM-19可使NPC细胞中MMP-9的mRNA和蛋白质表达下调,并降低细胞的侵润能力.研究结果表明,人滋养层细胞中存在ADAM-19表达的旁分泌调节机制,而ADAM-19在调节滋养层细胞侵润中发挥一定作用.这一结果为阐明ADAM-19在胎盘发生中的功能提供了新的科学资料.

Human ADAM-19 is a newly identified member of ADAM family, and is highly expressed in human placenta. But its functions in human trophoblast cells invasion have yet to be elucidated. A well-accepted human trophoblast cell model, NPC cell line, was used as in vitro model to investigate the influence ofhADAM-19 on cell invasion in human trophoblasts. The regulation of hADAM-19 expression by transforming growth factor β1 （TGF-β1） was investigated by RT-PCR and Western blotting. It was shown that over-expression of hADAM-19 in NPC cells led to down-regulation of MMP-9, MMP-2 mRNA expression and decrease in cell invasion. In NPC cells, the expression of hADAM-19 was significantly up-regulated by TGF-β1 in a dose-dependent manner. The data indicated that there existed paracrine regulation of ADAM-19 in human placenta. ADAM-19 was involved in invasion-inhibiting regulation of human trophoblast cells, and it may function, at least in part, through coordination with various MMPs.