PTEN对子痫前期中滋养细胞侵袭和血管生成的影响

Effects of PTEN on Trophoblast Invasion and Angiogenesis in Preeclampsia

为检查子痫前期患者胎盘样本中PTEN的表达模式,以及PTEN对滋养细胞侵袭和血管生成的可能调节作用,本研究采用RT-PCR、Western blotting和免疫组化方法检测PTEN在胎盘组织中的表达和定位。通过对HTR8/SVneo细胞转染过表达PTEN的pcDNA3.1重组质粒或靶向PTEN的siRNA来上调或下调PTEN的表达。采用Western blotting检测胎盘组织和细胞中缺氧诱导因子-1α(HIF-1α)、HIF-2α和血管内皮生长因子(VEGF)的表达。通过Matrigel Transwell测定法和Matrigel血管生成测定法检测滋养细胞的侵袭和血管生成能力。结果显示,与正常胎盘相比,子痫前期胎盘中PTEN的m RNA和蛋白表达水平均显著升高,而HIF-1α、HIF-2α和VEGF的蛋白表达水平均显著降低。PTEN的过表达显著抑制了HTR8/SVneo细胞的侵袭和血管生成,而下调PTEN的表达则促进了细胞侵袭和血管生成。PTEN的过表达显著抑制了HTR8/SVneo细胞中HIF-1α、HIF-2α和VEGF的蛋白表达,下调PTEN的表达则促进了HIF-1α、HIF-2α和VEGF的蛋白表达。本研究表明PTEN在子痫前期胎盘中过表达,PTEN的过表达抑制了滋养细胞的侵袭和血管生成能力,研究结果为揭示子痫前期发生发展的分子机制提供帮助。

In order to examine the expression pattern of PTEN in the placenta samples of patients with preeclampsia and the possible regulatory effect of PTEN on trophoblast invasion and angiogenesis,in this stugy,RT-PCR,Western blotting and immunohistochemistry were used to detect the expression and localization of PTEN in placental tissue.HTR8/SVneo cells were transfected with pcDNA3.1 overexpressing PTEN recombinant plasmid or PTEN targeting siRNA to up-regulate or down-regulate PTEN expression.Western blotting was used to detect the expression of hypoxia-inducible factor-1α(HIF-1α),HIF-2αand vascular endothelial growth factor(VEGF)in placental tissues and cells.The invasion of trophoblast cells and the ability of angiogenesis were detected by Matrigel Transwell assay and Matrigel angiogenesis assay.The results showed that compared with normal placenta,the mRNA and protein expression levels of PTEN in preeclamptic placenta were significantly increased,and the protein expression levels of HIF-1α,HIF-2αand VEGF were significantly reduced.Overexpression of PTEN significantly inhibited the invasion and angiogenesis of HTR8/SVneo cells,while down-regulation of PTEN expression promoted cell invasion and angiogenesis.Overexpression of PTEN significantly inhibited the protein expression of HIF-1α,HIF-2αand VEGF in HTR8/SVneo cells,and down-regulation of PTEN expression promoted the protein expression of HIF-1α,HIF-2αand VEGF.This study shows that PTEN is overexpressed in the placenta of preeclampsia,and the overexpression of PTEN inhibits the invasion and angiogenesis of trophoblast cells,and the results of provide help to reveal the molecular mechanism of the occurrence and development of preeclampsia.