Fibroblast growth factor-2 and fibroblast growth factor receptor-1 mRNA expression and peptide localization in placentae from normal and diabetic pregnancies
Fibroblast growth factor-2 and fibroblast growth factor receptor-1 mRNA expression and peptide localization in placentae from normal and diabetic pregnancies
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DOI：
10.1016/s0143-4004(98)90001-7
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发表时间：
1998-03-01
期刊：
影响因子：
3.8
通讯作者：
Hill, DJ
中科院分区：
文献类型：
--
作者：
Arany, E;Hill, DJ
成纤维细胞生长因子-2(成纤维细胞生长因子-2)是一种强有力的有丝分裂原，在胚胎发育过程中和胎儿组织中广泛表达。它被认为是一种内皮细胞有丝分裂原，在体内是血管生成的。在人足月胎盘和胎盘组织中也发现了成纤维细胞生长因子-2mRNA的表达，提示其在胎盘生长包括血管生成中起重要作用。本研究的目的是定量和定位成纤维细胞生长因子-2及其高亲和力受体FGFR1在正常足月妊娠(n=8，39-42周)和妊娠合并妊娠期1型糖尿病(n=8，36-40周)胎盘中的表达部位。分娩后立即收集组织，用于快速冷冻提取RNA，或使用S-35标记的编码人成纤维细胞生长因子-2或成纤维细胞生长因子1的CRNAs进行原位杂交，或使用抗人成纤维细胞生长因子-2或成纤维细胞生长因子1抗体进行免疫细胞化学。Northern印迹杂交显示，成纤维细胞生长因子-2和成纤维细胞生长因子受体1的mRNAs丰度显著增加。糖尿病妇女的胎盘与正常妇女的胎盘进行比较。正常足月胎盘绒毛组织、血管内皮细胞和合体滋养层细胞中均有少量表达。糖尿病患者胎盘合体滋养层细胞和绒毛组织中均有较丰富的成纤维细胞生长因子-2的表达。FGFR1的信使RNA与编码成纤维细胞生长因子-2的信使RNA的分布相似。免疫细胞化学显示绒毛血管内皮细胞中有丰富的成纤维细胞生长因子-2和FGFR1多肽，并与对照组胎盘间质组织的细胞膜有关。足月合体滋养层细胞内有少量阳性表达的FGF2。在合并糖尿病的妊娠中，合体滋养层细胞中还可见FGFR1和成纤维细胞生长因子2的强阳性表达。结果提示，作为一种自分泌剂，成纤维细胞生长因子-2促进胎盘血管生成，但可能从合体释放到母体循环。在糖尿病妊娠的胎盘中表达升高，尤其与合体滋养层细胞有关。这提示胎盘是先前在糖尿病妊娠中所描述的升高的母体循环中的成纤维细胞生长因子-2的来源。(C)1998年W.B.桑德斯有限公司
Fibroblast growth factor-2 (FGF-2) is a potent mitogen expressed widely during embryogenesis and in tissues of the human fetus. It is recognized as an endothelial cell mitogen and is angiogenic in vivo. Expression of FGF-2 mRNA has also been shown within the human term placenta, and FGF-2 isolated from placental tissue, suggesting a role in placental growth including angiogenesis. The purpose of this study was to quantify and localize the sites of expression of FGF-2 and its high-affinity receptor, FGFR1, within placentae from normal term human pregnancies (n=8, 39-42 weeks), and pregnancies complicated by pregestational, type 1 diabetes (n=8, 36-40 weeks). Tissues were collected immediately following delivery and were either snap-frozen for RNA isolation, or fixed for either in situ hybridization using a S-35-labelled cRNAs encoding human FGF-2 or FGFR1, or immunocytochemistry using antibodies against human FGF-2 or FGFR1. Northern blot hybridization showed a significantly increased abundance of mRNAs for both FGF-2 and FGFR1. in placentae from diabetic women compared to those from normal women. In normal term placenta FGF-2 mRNA was present at low abundance in fetal villous tissue, in the vascular endothelium of blood vessels, and in the syncytiotrophoblast. FGF-2 mRNA was considerably more abundant in the syncytiotrophoblast and villous tissue of placentae from diabetic patients. Messenger RNA for FGFR1 was similarly distributed to that encoding FGF-2. Immunocytochemistry revealed abundant FGF-2 and FGFR1 peptides in villous vascular endothelial cells, and associated with the cell membranes of stromal tissues in placentae from control pregnancies. Little immunoreactive FGF-2 was present in the syncytiotrophoblast at term. In pregnancies complicated by diabetes intense staining for immunoreactive FGF-2 and for FGFR1 additionally existed in syncytiotrophoblast. The results suggest that FGF-2 acting as an autocrine agent contributes to placental angiogenesis, but may be released from the syncytium into the maternal circulation. Expression is elevated in placentae from diabetic pregnancies, and is particularly associated with the syncytiotrophoblast. This suggests a placental source for the elevated circulating maternal FGF-2 previously described in diabetic pregnancy. (C) 1998 W.B. Saunders Company Ltd.