Effects of increased fetuin-A in human trophoblast cells and associated pregnancy outcomes

Effects of increased fetuin-A in human trophoblast cells and associated pregnancy outcomes
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DOI:
10.1016/j.ajog.2012.10.872
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发表时间:
2012-12-01
影响因子:
9.8
通讯作者:
Parry, Samuel
Parry, Samuel
中科院分区:
医学1区
文献类型:
--
作者:
Gomez, Luis M.;Anton, Lauren;Parry, Samuel

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目的:本研究的目的是确定胎儿蛋白a是否影响滋养细胞活力和侵袭,结合激活酪氨酸激酶受体的生长因子是否受到胎儿蛋白a的损害,以及母体血清胎儿蛋白a水平升高是否与不良妊娠结局相关。研究设计:我们研究了妊娠早期暴露于胎儿素a、胰岛素样生长因子和胎盘生长因子的外滋养细胞的活力和侵袭。评估胰岛素受体底物的表达。我们比较了111例子痫前期患者和95例对照组的血清胎儿素a水平。结果:在存在或不存在生长因子的情况下,胎蛋白a降低了外滋养细胞的活力和侵袭性。在胰岛素样生长因子处理过的上皮外滋养细胞中,Fetuin-A降低胰岛素受体底物-1的表达,酪氨酸磷酸化胰岛素受体底物-1的表达。即使在我们控制了糖尿病、高血压和肥胖之后,子痫前期患者的血清胎儿素a水平升高也比对照组更为普遍。结论:胎儿素a可能通过抑制受体酪氨酸激酶活性而降低滋养细胞活力和侵袭。血清中胎儿素a水平升高可能与子痫前期有关。
OBJECTIVE: The purpose of this study was to determine whether fetuin-A affects trophoblast viability and invasion, whether growth factors that bind receptors that activate tyrosine kinase are impaired by fetuin-A, and whether elevated maternal serum fetuin-A levels are associated with adverse pregnancy outcomes.STUDY DESIGN: We studied viability and invasion in first-trimester extravillous trophoblast cells that were exposed to fetuin-A, insulin-like growth factor, and placental growth factor. Insulin receptor substrates expression was assessed. We compared serum fetuin-A levels in 111 preeclampsia cases and 95 controls.RESULTS: Fetuin-A reduced extravillous trophoblast cell viability and invasion in the presence or absence of growth factors. Fetuin-A reduced insulin receptor substrate-1 and tyrosine phosphorylated insulin receptor substrate-1 expression in extravillous trophoblast cells that had been treated with insulin-like growth factor. Elevated serum fetuin-A levels were more prevalent in preeclampsia cases than control subjects, even after we controlled for diabetes mellitus, hypertension, and obesity.CONCLUSION: Fetuin-A may decrease trophoblast viability and invasion caused by the inhibition of receptor tyrosine kinase activity. Elevated serum levels of fetuin-A may be associated with preeclampsia.