Placental productions and expressions of soluble endoglin, soluble fms-like tyrosine kinase receptor-1, and placental growth factor in normal and preeclamptic pregnancies
Placental productions and expressions of soluble endoglin, soluble fms-like tyrosine kinase receptor-1, and placental growth factor in normal and preeclamptic pregnancies
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DOI：
10.1210/jc.2007-1550
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发表时间：
2008-01-01
影响因子：
5.8
通讯作者：
Wang, Yuping
中科院分区：
文献类型：
--
作者：
Gu, Yang;Lewis, David F.;Wang, Yuping
内容：抗血管生成因子可溶性内皮糖蛋白（sEng）和可溶性fms样酪氨酸激酶受体-1（sFlt-1）在子痫前期（PE）的病理生理学中的表达增加。我们的目的是确定正常和PE胎盘之间的胎盘球蛋白（Eng）、fms样酪氨酸激酶受体-1（Flt-1）和胎盘生长因子（PlGF）表达的差异，以及sEng、sFlt-1、方法：分离自正常和PE胎盘的滋养层细胞（TC），分别在常规氧（5%CO2/空气）和低氧（2%O2/5%CO2/93%N2）条件下培养。通过ELISA测定sEng、sFlt-1和PlGF的产生。采用免疫组化和Western blot分析胎盘组织中Eng、Flt-1和PIGF的蛋白表达。结果：与正常胎盘组织相比，PE组胎盘组织中sEng、sFlt-1和PlGF的表达均显著增加（P < 0.05）。在低氧条件下，PETC而不是正常TC释放更多的sEng和sFlt-1。而正常和PE TC释放PIGF均较低（P < 0.05）。在PE胎盘中观察到Eng和Flt-1以及糖基化Eng和Flt-1的表达增强。免疫印迹还显示，TC释放糖基化的sFlt-1，但不是sEng，在culture.Conclusions：PE TC产生更多的sEng，sFlt-1，和PIGF比正常TC。低氧条件促进sEng和sFlt-1，但减少PE TC的PlGF生成。PE胎盘中存在更多糖基化的sEng和sFlt-1。在培养物中，滋养层细胞释放糖基化的sFlt-1，但未糖基化的sEng。
Context: Increased production of antiangiogenic factors soluble endoglin (sEng) and soluble fms-like tyrosine kinase receptor-1 (sFlt-1) by the placenta contributes to the pathophysiology in pre-eclampsia (PE).Objective: Our objective was to determine the differences in encloglin (Eng), fms-like tyrosine kinase receptor-1 (Flt-1), and placental growth factor (PIGF) expressions between normal and PE placentas and sEng, sFlt-1, and PlGF production by trophoblast cells (TC) cultured under lowered oxygen conditions.Methods:TCs isolated from normal and PE placentas were cultured under regular(5% CO2/air) and lowered (2% O-2/5% CO2/93% N-2) oxygen conditions. sEng, sFlt-1, and PIGF productions were determined by ELISA. Protein expressions for Eng, Flt-1, and PIGF in the placental tissues were accessed by immunohistochemical staining and Western blot analysis. Deglycosylated Eng, Flt-1, and PlGF protein expressions in placental tissues were also examined.Results: PE TCs produced significantly more sEng, sFlt-1, and PIGF compared with those from normal TCs (P < 0.05). Under lowered oxygen conditions, PETCs, but not normal TCs, released more sEng and sFlt-1. In contrast, both normal and PE TCs released less PIGF (P < 0.05). Enhanced expressions of Eng and Flt-1, as well as glycosylated Eng and Flt-1, were observed in PE placentas. Immunoblot also revealed that TCs released glycosylated sFlt-1, but not sEng, in culture.Conclusions: PE TCs produce more sEng, sFlt-1, and PIGF than normal TCs. Lowered oxygen conditions promote sEng and sFlt-1, but reduce PIGF, productions by PE TCs. More glycosylated sEng and sFlt-1 are present in PE placentas. Trophoblasts release glycosylated sFlt-1, but unglycosylated sEng, in culture.