Colocalization of acidic and basic fibroblast growth factor (FGF) in human placenta and the cellular effects of bFGF in trophoblast cell line JEG-3.
Colocalization of acidic and basic fibroblast growth factor (FGF) in human placenta and the cellular effects of bFGF in trophoblast cell line JEG-3.
复制标题
酸性和碱性成纤维细胞生长因子 (FGF) 在人胎盘中的共定位以及 bFGF 在滋养层细胞系 JEG-3 中的细胞作用。
作者：
R. Ferriani;A. Ahmed;A. Sharkey;S. Smith
胎盘经历广泛的血管生成和细胞增殖，以建立足够的血液供应给胎儿。本研究的目的是比较和对比酸性和碱性成纤维细胞生长因子（FGF）在早期妊娠和足月胎盘和妊娠蜕膜的免疫定位。以人绒毛膜癌细胞系JEG-3为细胞滋养层模型，研究碱性成纤维细胞生长因子对细胞增殖及磷脂酶C、D活性的影响。采用兔抗人碱性成纤维细胞生长因子（FGF）免疫组化方法，在孕早期胎盘细胞滋养层细胞及其周围和绒毛外滋养层细胞中检测到基本的FGF免疫反应性（IR）。酸性FGF抗体产生相同的染色模式，表明酸性FGF和碱性FGF的共定位。足月时，胎盘绒毛周围的合体滋养细胞染色较弱且较弥散，中、大型胎盘血管的平滑肌细胞和一些内皮细胞染色较强。早孕期蜕膜内内皮细胞和绒毛外滋养层细胞染色较强，而腺上皮染色较弱。碱性FGF以剂量依赖性方式诱导JEG-3细胞中的[3 H]胸苷掺入，并导致在用类似浓度的肌-[3 H]肌醇预标记的细胞中肌醇磷酸积累增加，表明磷脂酶C在JEG-3细胞增殖中的作用。然而，碱性成纤维细胞生长因子未能刺激磷脂酶D活性的细胞预先标记的[3 H]肉豆蔻酸。酸性FGF和碱性FGF的检测在母体和胎儿侧的胎盘在妊娠早期表明FGF在血管生成中的作用，而本地化的生长因子在长期，广泛的血管生成减少时，将表明FGF可能与滋养层的分化功能。碱性成纤维细胞生长因子的核定位在分裂，但不分裂的胎盘细胞与碱性成纤维细胞生长因子对JEF-3细胞的影响，强烈支持碱性成纤维细胞生长因子在细胞滋养层细胞增殖在体内的作用。
The placenta undergoes extensive angiogenesis and cellular proliferation to establish adequate blood supply to the fetus. The aim of this study was to compare and contrast the immunolocalization of acidic and basic fibroblast growth factor (FGF) in both first trimester and term placenta and gestational decidua. Human choriocarcinoma cell line JEG-3 were employed as a model of cytotrophoblast and the effect of basic FGF on cell proliferation and phospholipase C and D activation investigated. Basic FGF-immunoreactivity (IR) was detected in or around cytotrophoblast cells and in extravillous trophoblast in first trimester placenta by immunohistochemistry using primary polyclonal rabbit antibodies. Identical staining patterns were produced by acidic FGF antibodies indicating colocalization of acidic FGF and basic FGF. At term, weaker and more diffuse staining was seen in the syncytiotrophoblast surrounding the placenta villi and strong staining was present in the smooth muscle cells of mid and large size placental vessels and in some endothelial cells. Endothelial cells and extravillous trophoblast stained strongly within the decidua at first trimester, whereas the glandular epithelium was weakly stained. Basic FGF induced [3H]thymidine incorporation in JEG-3 cells in a dose dependent manner and caused an increase in inosital phosphate accumulation in cells pre-labelled with myo-[3H]inosital at similar concentrations, suggesting a role of phospholipase C in JEG-3 cell proliferation. However, basic FGF failed to stimulate phospholipase D activity in cells pre-labelled with [3H]myristic acid. The detection of acid FGF and basic FGF on both maternal and fetal side of the placenta during early pregnancy suggests a role for FGF in angiogenesis, whereas localisation of the growth factor at term, when extensive angiogenesis has diminished, would indicate that FGF may be associated with more differentiated functions of the trophoblast. The nuclear localization of basic FGF in dividing but not non-dividing placental cells together with the effect of basic FGF on JEF-3 cells, strongly supports a role for basic FGF in cytotrophoblast proliferation in vivo.