TLR9 (Toll-Like Receptor 9) Agonist Suppresses Angiogenesis by Differentially Regulating VEGFA (Vascular Endothelial Growth Factor A) and sFLT1 (Soluble Vascular Endothelial Growth Factor Receptor 1) in Preeclampsia
TLR9 (Toll-Like Receptor 9) Agonist Suppresses Angiogenesis by Differentially Regulating VEGFA (Vascular Endothelial Growth Factor A) and sFLT1 (Soluble Vascular Endothelial Growth Factor Receptor 1) in Preeclampsia
复制标题
TLR9（Toll 样受体 9）激动剂通过差异调节先兆子痫患者的 VEGFA（血管内皮生长因子 A）和 sFLT1（可溶性血管内皮生长因子受体 1）来抑制血管生成
DOI：
10.1161/hypertensionaha.117.10510
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发表时间：
2018-04-01
期刊：
影响因子：
8.3
通讯作者：
Cheng, Weiwei
中科院分区：
文献类型：
--
作者：
He, Biwei;Yang, Xingyu;Cheng, Weiwei
先兆子痫是一种常见的妊娠特有疾病，其特征是血压升高和蛋白尿。母体免疫系统的激活和胎盘血管生成受损被认为是先兆子痫的发病机制之一。TLR9(Toll样受体9)在先天免疫中发挥作用，保护机体免受感染。本研究的目的是确定在子痫前期条件下，TLR9是否抑制母胎界面的血管生成。我们证实了子痫前期患者胎盘中VEGFA(血管内皮生长因子A)的下调和TLR9和sFLT1(可溶性血管内皮生长因子受体1)的上调。然后，我们使用合成的TLR9激动剂CpG(胞苷-磷酸-鸟苷)-ODN(寡核苷酸；ODN1826)建立了一种具有先兆子痫症状的小鼠模型。我们观察了先兆子痫样动物模型胎盘和经CpG-ODN处理的滋养层细胞中VEGFA的下调和sFLT1的上调(ODN2006)。此外，沉默TLR9可促进HTR8/SVneo细胞的迁移和侵袭。综上所述，TLR9能够通过差异调节VEGFA和sFlt1在母胎界面的表达而有力地抑制血管生成，从而可能促进先兆子痫的发生。
Preeclampsia is a common pregnancy-specific disorder characterized by elevated blood pressure and proteinuria. Activation of the maternal immune system and impaired placental angiogenesis are thought to contribute to the pathogenesis of preeclampsia. TLR9 (Toll-like receptor 9) plays a role in innate immunity, defending the organism against infection. The purpose of this study was to determine whether TLR9 inhibits angiogenesis at the fetomaternal interface under conditions of preeclampsia. We confirmed the downregulation of VEGFA (vascular endothelial growth factor A) and upregulation of TLR9 and sFLT1 (soluble vascular endothelial growth factor receptor 1) in placentas from preeclamptic women. Then, we established a mouse model with preeclampsia-like symptoms using the synthetic TLR9 agonist CpG (cytidine–phosphate–guanosine)-ODN (oligodeoxynucleotide; ODN1826). We observed the downregulation of VEGFA and the upregulation of sFLT1 in placentas from the preeclampsia-like animal model and in trophoblasts treated with CpG-ODN (ODN2006). In addition, silencing TLR9 promoted the migration and invasion of HTR8/SVneo cells. In conclusion, TLR9 is capable of robustly suppressing angiogenesis by differentially regulating the expression of VEGFA and sFLT1 at the fetomaternal interface, potentially contributing to the development of preeclampsia.