Luo Jianying, Qiao Fuyuan, Yin Xianghua
Department of Obstetrics and Gynecology, Northern Jiangsu Province Hospital, Clinical Medical College, Yangzhou University, Jiangsu, China.
J Reprod Dev. 2011 Feb;57(1):84-91. doi: 10.1262/jrd.10-008k. Epub 2010 Oct 28.
The role of fibroblast growth factor 2 (FGF2) secretion by vascular endothelial cells during trophoblast invasion was assessed. The human extravillous trophoblast cell line, TEV-1, and umbilical vein endothelial cell line, HUVE-12, were cocultured under normal and hypoxic conditions. FGF2 expression in HUVE-12 cells and matrix metalloproteinase 9 (MMP9) and tissue inhibitor of metalloproteinase 1 (TIMP1) expression in TEV-1 cells were analyzed using quantitative RT-PCR and Western blot analyses. TEV-1 cell invasion was also examined. FGF2 expression in the HUVE-12 cells cocultured with TEV-1 cells was significantly increased under hypoxic conditions. In the TEV-1 cells cocultured with HUVE-12, hypoxia reduced MMP9 expression and increased TIMP1 expression; it also reduced cell invasion by 43%. However, the expression of MMP9 and TIMP1 and ratio of MMP9/TIMP1 were increased when the TEV-1 cells were cultured alone under hypoxic conditions. These findings suggest that FGF2 release by stressed endothelial cells of uterine spiral arteries play roles in decreasing MMP9 and increasing TIMP1 production in extravillous trophoblasts (EVT) in response to stress, resulting in reduced EVT invasion and possibly shallow implantation of the placenta.
评估了滋养层细胞侵袭过程中血管内皮细胞分泌成纤维细胞生长因子2（FGF2）的作用。在正常和缺氧条件下，将人绒毛外滋养层细胞系TEV-1和脐静脉内皮细胞系HUVE-12进行共培养。使用定量逆转录聚合酶链反应（RT-PCR）和蛋白质免疫印迹分析来检测HUVE-12细胞中FGF2的表达以及TEV-1细胞中基质金属蛋白酶9（MMP9）和金属蛋白酶组织抑制剂1（TIMP1）的表达。同时也检测了TEV-1细胞的侵袭能力。在缺氧条件下，与TEV-1细胞共培养的HUVE-12细胞中FGF2的表达显著增加。在与HUVE-12共培养的TEV-1细胞中，缺氧降低了MMP9的表达并增加了TIMP1的表达；其细胞侵袭能力也降低了43%。然而，当TEV-1细胞在缺氧条件下单独培养时，MMP9和TIMP1的表达以及MMP9/TIMP1的比值增加。这些研究结果表明，子宫螺旋动脉应激的内皮细胞释放的FGF2在应激反应中对降低绒毛外滋养层细胞（EVT）中MMP9的产生和增加TIMP1的产生发挥作用，从而导致EVT侵袭减少以及胎盘可能植入过浅。
