Tse W K, Whitley G St J, Cartwright J E
Department of Biochemistry and Immunology, St George's Hospital Medical School, Cranmer Terrace, London, SW17 0RE, UK.
Placenta. 2002 Nov;23(10):699-705. doi: 10.1016/s0143-4004(02)90866-0.
During placental development extravillous trophoblasts invade the uterine wall in a tightly regulated manner dependent on both pro- and anti-invasive molecules. We have shown using the extravillous trophoblast cell line, SGHPL-4, that both cellular invasion and motility are stimulated by hepatocyte growth factor (HGF). It has previously been demonstrated that transforming growth factor=beta1 (TGF-beta1), produced by the decidua, inhibits extravillous trophoblast proliferation and invasion. It was the aim of this study to determine whether TGF-beta1 could modulate HGF-induced motility and invasion and, if so, examine the mechanism involved. TGF-beta1 significantly inhibited the growth of SGHPL-4 cells stimulated with 10 per cent serum. HGF-stimulated trophoblast cell invasion and motility were significantly inhibited by TGF-beta1. Neither HGF nor TGF-beta1 had an effect on SGHPL-4 cell growth under the conditions used for the invasion and motility experiments (0.5 per cent serum). Previous studies suggest that both HGF-stimulated trophoblast invasion and motility may be regulated by the production of nitric oxide. TGF-beta1 was found to significantly decrease HGF-induced iNOS expression therefore suggesting a novel mechanism by which TGF-beta1 could regulate motility and invasion.
在胎盘发育过程中,绒毛外滋养层细胞以一种严格调控的方式侵入子宫壁,这依赖于促侵入分子和抗侵入分子。我们使用绒毛外滋养层细胞系SGHPL-4已表明,肝细胞生长因子(HGF)可刺激细胞的侵入和运动。先前已证实,由蜕膜产生的转化生长因子β1(TGF-β1)可抑制绒毛外滋养层细胞的增殖和侵入。本研究的目的是确定TGF-β1是否能调节HGF诱导的运动和侵入,如果可以,则研究其中涉及的机制。TGF-β1显著抑制了用10%血清刺激的SGHPL-4细胞的生长。TGF-β1显著抑制了HGF刺激的滋养层细胞的侵入和运动。在用于侵入和运动实验的条件下(0.5%血清),HGF和TGF-β1对SGHPL-4细胞的生长均无影响。先前的研究表明,HGF刺激的滋养层细胞的侵入和运动可能都受一氧化氮产生的调节。发现TGF-β1可显著降低HGF诱导的诱导型一氧化氮合酶(iNOS)表达,因此提示了一种TGF-β1调节运动和侵入的新机制。