滋养层
基质金属蛋白酶
整合素
肿瘤坏死因子α
细胞生物学
受体
男科
纤溶酶原激活剂
化学
生物
分子生物学
内科学
内分泌学
胎盘
医学
胎儿
怀孕
遗传学
作者
Bei Xu,Shirley Nakhla,Angela Makris,Annemarie Hennessy
出处
期刊:Placenta
[Elsevier]
日期:2011-03-01
卷期号:32 (3): 241-246
被引量:64
标识
DOI:10.1016/j.placenta.2010.12.005
摘要
Preeclampsia has been linked to shallow trophoblast invasion and failure of uterine spiral artery transformation. Interaction between trophoblast cells and maternal uterine endothelium is critically important for this remodelling. The aim of our study was to investigate the effect of TNF-α on the interactions of trophoblast-derived JEG-3 cells into capillary-like cellular networks. We have employed an in vitro trophoblast-endothelial cell co-culture model to quantify trophoblast integration into endothelial cellular networks and to investigate the effects of TNF-α. Controlled co-cultures were also treated with anti-TNF-α antibody (5 μg/ml) to specifically block the effect of TNF-α. The invasion was evaluated by performing quantitative PCR (Q-PCR) to analyse gene expression of matrix metalloproteinases-2 (MMP-2), MMP-9, tissue inhibitor of matrix metalloproteinase (TIMP)-1, integrins (α1β1 and α6β4), plasminogen activator inhibitor (PAI)-1, E-cadherin and VE-cadherin. JEG-3 cell integration into endothelial networks was significantly inhibited by exogenous TNF-α. The inhibition was observed in the range of 0.2–5 ng/ml, to a maximum 56% inhibition at the highest concentration. This inhibition was reversed by anti-TNF-α antibody. Q-PCR analysis showed that mRNA expression of integrins α1β1 and MMP-2 was significantly decreased. VE-cadherin mRNA expression was significantly up-regulated (32–80%, p < 0.01) but its protein concentration in the cell lysates was significantly reduced (20–45%, p < 0.01). PAI-1, MMP-9, TIMP-1 and E-cadherin were not affected. In conclusion, TNF-α can inhibit trophoblast-like cells (JEG-3) integration into maternal endothelial cellular networks, and this process involves the inhibition of MMP-2 and a failure of integrins switch from α6β4 to α1β1. These molecular correlations reflect the changes identified in human preeclampsia.
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