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蛋白酪氨酸磷酸酶抑制剂诱导滋养层细胞融合

Induction of trophoblast cell fusion by a protein tyrosine phosphatase inhibitor.

作者信息

Vargas A, Moreau J, Le Bellego F, Lafond J, Barbeau B

机构信息

Département des Sciences Biologiques and BioMed Research Center, Université du Québec à Montréal, 2080 St-Urbain, Montréal, QC, H2X 3X8, Canada.

出版信息

Placenta. 2008 Feb;29(2):170-4. doi: 10.1016/j.placenta.2007.10.012.

Abstract

In the placenta, trophoblast cell fusion leads to the formation of the syncytiotrophoblast, which plays an essential role in the diffusion of nutrients and hormones from the mother to the fetus. Different protein tyrosine kinases are involved in the modulation of this biological process. Herein, we investigated the impact of a protein tyrosine phosphatase (PTP) inhibitor (bpV[pic]) on trophoblast fusion. Upon bpV[pic] or forskolin treatment, primary and BeWo trophoblastic cells demonstrated higher cAMP levels and a more potent induction of cell fusion, while non-fusogenic JEG-3 cells were non-responsive to these treatments. RT-PCR analyses on stimulated BeWo cells or primary cytotrophoblast cells demonstrated an increase in syncytin-1 mRNA levels, which was more pronounced upon forskolin/bpV[pic] treatment. Using the luciferase gene upstream of the syncytin-1 promoter, similar results were obtained in BeWo cells after stimulation. These results demonstrate that PTPs act negatively on cell fusion in human trophoblasts and could control the timing of syncytiotrophoblast formation during placenta development.

摘要

在胎盘中,滋养层细胞融合导致合体滋养层的形成,合体滋养层在营养物质和激素从母体向胎儿的扩散过程中发挥着重要作用。不同的蛋白酪氨酸激酶参与了这一生物学过程的调节。在此,我们研究了一种蛋白酪氨酸磷酸酶(PTP)抑制剂(bpV[pic])对滋养层融合的影响。在用bpV[pic]或福斯高林处理后,原代滋养层细胞和BeWo滋养层细胞表现出更高的环磷酸腺苷(cAMP)水平以及更强的细胞融合诱导作用,而非融合性的JEG-3细胞对这些处理无反应。对受刺激的BeWo细胞或原代细胞滋养层细胞进行逆转录聚合酶链反应(RT-PCR)分析显示,合体素-1信使核糖核酸(mRNA)水平升高,在福斯高林/bpV[pic]处理后更为明显。使用合体素-1启动子上游的荧光素酶基因,在刺激后的BeWo细胞中也得到了类似结果。这些结果表明,蛋白酪氨酸磷酸酶对人滋养层细胞融合起负向作用,并可能在胎盘发育过程中控制合体滋养层形成的时间。

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