Chung I B, Yelian F D, Zaher F M, Gonik B, Evans M I, Diamond M P, Svinarich D M
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Placenta. 2000 May;21(4):320-4. doi: 10.1053/plac.1999.0481.
Embryo implantation and development are critically dependent upon the spatial and temporal regulation of angiogenesis and localized vascular permeability. A key mediator of these effects is the endothelial cell mitogen vascular endothelial growth factor (VEGF). VEGF has been shown to promote endometrial vascular permeability, fetal vasculogenesis and placental, fetal and maternal angiogenesis. However, the mechanism through which this regulation occurs in the placenta is poorly understood. This study was conducted to determine if the pro-angiogenic cytokines, TNF-alpha and TGF-beta1, affect VEGF expression in human first trimester trophoblasts. Culture of a first trimester trophoblast cell line (HTR-8/SVneo), in the presence of either TNF-alpha or TGF-beta1, resulted in the expression of significant levels of VEGF in culture. The trophoblast cell line also showed a time-dependent and a dose-dependent increase in VEGF mRNA levels when cultured in the presence of either TNF-alpha or TGF-beta1. These results suggest that both TNF-alpha and TGF-beta1 may regulate the production of VEGF in early gestational trophoblasts and may therefore serve to modulate placental vascular permeability and angiogenesis that are necessary for embryo implantation and placentation.
胚胎着床与发育严重依赖于血管生成及局部血管通透性的空间和时间调控。这些作用的一个关键介质是内皮细胞促有丝分裂原血管内皮生长因子（VEGF）。VEGF已被证明可促进子宫内膜血管通透性、胎儿血管生成以及胎盘、胎儿和母体的血管生成。然而，胎盘内这种调控发生的机制却知之甚少。本研究旨在确定促血管生成细胞因子TNF-α和TGF-β1是否影响人早孕滋养层细胞中VEGF的表达。在TNF-α或TGF-β1存在的情况下培养早孕滋养层细胞系（HTR-8/SVneo），导致培养物中VEGF大量表达。当在TNF-α或TGF-β1存在的情况下培养时，滋养层细胞系的VEGF mRNA水平也呈现出时间依赖性和剂量依赖性增加。这些结果表明，TNF-α和TGF-β1均可能调节早孕滋养层细胞中VEGF的产生，因此可能有助于调节胚胎着床和胎盘形成所必需的胎盘血管通透性和血管生成。
