Thrombin regulates soluble fms-like tyrosine kinase-1 (sFlt-1) expression in first trimester decidua - Implications for preeclampsia
Thrombin regulates soluble fms-like tyrosine kinase-1 (sFlt-1) expression in first trimester decidua - Implications for preeclampsia
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DOI：
10.2353/ajpath.2007.060465
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发表时间：
2007-04-01
影响因子：
6
通讯作者：
Schatz, Frederick
中科院分区：
文献类型：
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作者：
Lockwood, Charles J.;Toti, Paolo;Schatz, Frederick
先兆子痫的主要胎盘缺陷是滋养细胞对蜕膜的浅侵入，导致血管转化不完全和子宫胎盘灌注不足。可溶性fms样酪氨酸激酶-1（sFlt-1）似乎通过抑制局部血管生成和/或阻碍滋养层细胞侵袭来干扰这些事件。先兆子痫还与母体血栓形成倾向和蜕膜出血有关，后者由蜕膜细胞表达的组织因子形成凝血酶。虽然sFlt-1是高度表达的滋养层，sFlt-1的表达尚未研究在蜕膜细胞，这是主要的细胞类型遇到的入侵滋养层。在这里，我们证明，分离的蜕膜细胞表达sFlt-1 mRNA，这表明它们可以合成sFlt-1。此外，在孕早期蜕膜细胞中，凝血酶增强sFlt-1 mRNA水平，通过定量逆转录-聚合酶链反应测定，和分泌的sFlt-1蛋白水平，通过酶联免疫吸附试验测定。凝血酶拮抗剂水蛭素阻断了这种作用，表明活性凝血酶是必需的。强调凝血酶反应的特异性，无论是白细胞介素-1 β还是肿瘤坏死因子-α都不影响蜕膜细胞中的sFlt-1表达。与早孕期蜕膜相反。细胞，凝血酶不影响培养的长期蜕膜细胞sFlt-1水平。在妊娠早期，凝血酶可作为蜕膜细胞sFlt-1表达自分泌/旁分泌增强剂，通过干扰局部血管转化促进先兆子痫。
The primary placental defect in preeclampsia is shallow trophoblast invasion of the decidua leading to incomplete vascular transformation and inadequate uteroplacental perfusion. Soluble fms-like tyrosine kinase-1 (sFlt-1) seems to interfere with these events by inhibiting local angiogenesis and/or by impeding trophoblast invasion. Preeclampsia is also associated with maternal thrombophilias and decidual hemorrhage, which form thrombin from decidual cell-expressed tissue factor. Although sFlt-1 is highly expressed by trophoblasts, sFlt-1 expression has not been studied in decidual cells, which are the predominant cell type encountered by invading trophoblasts. Here, we demonstrate that isolated decidual cells express sFlt-1 mRNA, suggesting that they can synthesize sFlt-1. Moreover, in first trimester decidual cells, thrombin enhanced sFlt-1 mRNA levels, as measured by quantitative reverse transcriptase-polymerase chain reaction, and levels of secreted sFlt-1 protein, as measured by enzyme-linked immunosorbent assay. The thrombin antagonist hirudin blocked this effect, demonstrating that active thrombin is required. Emphasizing the specificity of the thrombin response, neither interleukin-1 beta nor tumor necrosis factor-a affected sFlt-1 expression in the decidual cells. In contrast to first trimester decidual. cells, thrombin did not affect sFlt-1 levels in cultured term decidual cells. in early pregnancy, thrombin may act as an autocrine/paracrine enhancer of sFlt-1 expression by decidual cells to promote preeclampsia by interfering with local vascular transformation.