Gu Yang, Lewis David F, Wang Yuping
Department of Obstetrics and Gynecology, Louisiana State University Health Sciences Center-Shreveport, PO Box 33932, Shreveport, Louisiana 71130, USA.
J Clin Endocrinol Metab. 2008 Jan;93(1):260-6. doi: 10.1210/jc.2007-1550. Epub 2007 Oct 23.
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 preeclampsia (PE).
Our objective was to determine the differences in endoglin (Eng), fms-like tyrosine kinase receptor-1 (Flt-1), and placental growth factor (PlGF) expressions between normal and PE placentas and sEng, sFlt-1, and PlGF production by trophoblast cells (TC) cultured under lowered oxygen conditions.
TCs isolated from normal and PE placentas were cultured under regular (5% CO2/air) and lowered (2% O2/5% CO2/93% N2) oxygen conditions. sEng, sFlt-1, and PlGF productions were determined by ELISA. Protein expressions for Eng, Flt-1, and PlGF 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.
PE TCs produced significantly more sEng, sFlt-1, and PlGF compared with those from normal TCs (P < 0.05). Under lowered oxygen conditions, PE TCs, but not normal TCs, released more sEng and sFlt-1. In contrast, both normal and PE TCs released less PlGF (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.
PE TCs produce more sEng, sFlt-1, and PlGF than normal TCs. Lowered oxygen conditions promote sEng and sFlt-1, but reduce PlGF, 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.
胎盘产生的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）增加，参与了子痫前期（PE）的病理生理过程。
我们的目的是确定正常胎盘与PE胎盘之间内皮糖蛋白（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，以及在低氧条件下培养的滋养层细胞（TC）产生sEng、sFlt-1和PlGF的情况。
从正常胎盘和PE胎盘中分离出的TC在常规（5%二氧化碳/空气）和低氧（2%氧气/5%二氧化碳/93%氮气）条件下培养。通过酶联免疫吸附测定法（ELISA）测定sEng、sFlt-1和PlGF的产生量。通过免疫组织化学染色和蛋白质印迹分析来检测胎盘组织中Eng、Flt-1和PlGF的蛋白表达。还检测了胎盘组织中去糖基化的Eng、Flt-1和PlGF蛋白表达。
与正常TC相比，PE TC产生的sEng、sFlt-1和PlGF显著更多（P<0.05）。在低氧条件下，PE TC而非正常TC释放更多的sEng和sFlt-1。相反地，正常和PE TC释放的PlGF均减少（P<0.05）。在PE胎盘中观察到Eng和Flt-1以及糖基化的Eng和Flt-1表达增强。免疫印迹还显示，TC在培养过程中释放糖基化的sFlt-1，但不释放sEng。
PE TC比正常TC产生更多的sEng、sFlt-1和PlGF。低氧条件促进PE TC产生sEng和sFlt-1，但减少PlGF的产生。PE胎盘中存在更多糖基化的sEng和sFlt-1。滋养层细胞在培养过程中释放糖基化的sFlt-1，但不释放未糖基化的sEng。
