Shore V H, Wang T H, Wang C L, Torry R J, Caudle M R, Torry D S
Department of Obstetrics and Gynecology, University of Tennessee Graduate School of Medicine, Knoxville 37920, USA.
Placenta. 1997 Nov;18(8):657-65. doi: 10.1016/s0143-4004(97)90007-2.
The expression of the angiogenic growth factors, vascular endothelial cell growth factor (VEGF) and placenta growth factor (PIGF) was demonstrated in isolated human term cytotrophoblast and in vitro differentiated syncytiotrophoblast. RNase protection assays demonstrated VEGF expression in both cytotrophoblast and syncytiotrophoblast while prominent PIGF expression was detected in both types of trophoblast by Northern blot analyses. VEGF expression increased approximately eightfold in trophoblast cultured under hypoxic conditions (1 per cent O2) yet PIGF expression decreased 73 +/- 5.5 per cent in the same trophoblast. These results suggest distinct regulatory mechanisms govern expression of VEGF and PIGF in trophoblast. Characterization of the VEGF/PIGF receptors, KDR and flt-1, revealed the presence of flt-1 mRNA in isolated cytotrophoblast and in vitro differentiated syncytiotrophoblast. KDR was not detected in the isolated trophoblast. Exogenous rhVEGF induced c-Jun N-terminal kinase (JNK) activity in the normal trophoblast indicating that the flt-1 receptors on trophoblast are functional. Trophoblast-derived VEGF/PIGF could act in a paracrine fashion to promote uterine angiogenesis and vascular permeability within the placental bed. In addition, presence of function flt-1 on normal trophoblast suggests that VEGF/PIGF functions in an autocrine manner to perform an as yet undefined role in trophoblast invasion, differentiation, and/or metabolic activity during placentation.
在分离的足月人细胞滋养层细胞以及体外分化的合体滋养层细胞中证实了血管生成生长因子血管内皮细胞生长因子（VEGF）和胎盘生长因子（PIGF）的表达。核糖核酸酶保护试验证实细胞滋养层细胞和合体滋养层细胞中均有VEGF表达，而通过Northern印迹分析在这两种类型的滋养层细胞中均检测到显著的PIGF表达。在低氧条件（1% O₂）下培养的滋养层细胞中，VEGF表达增加了约8倍，而同一滋养层细胞中PIGF表达下降了73±5.5%。这些结果表明，滋养层细胞中VEGF和PIGF的表达受不同的调控机制支配。对VEGF/PIGF受体KDR和flt-1的特性分析显示，在分离的细胞滋养层细胞以及体外分化的合体滋养层细胞中存在flt-1 mRNA。在分离的滋养层细胞中未检测到KDR。外源性重组人VEGF诱导正常滋养层细胞中的c-Jun氨基末端激酶（JNK）活性，表明滋养层细胞上的flt-1受体具有功能。滋养层细胞衍生的VEGF/PIGF可能以旁分泌方式发挥作用，促进胎盘床内的子宫血管生成和血管通透性。此外，正常滋养层细胞上存在功能性flt-1表明，VEGF/PIGF以自分泌方式发挥作用，在胎盘形成过程中对滋养层细胞的侵袭、分化和/或代谢活性发挥尚未明确的作用。
