Preeclampsia, a pregnancy-specific disorder, is characterized by abnormal vascular remodeling of the spiral arteries due to deficient trophoblast invasion. Lipopolysaccharide (LPS) administration to pregnant rats on day 5 of pregnancy could induce excessive immune response at the maternal-fetal interface contributing to poor early placentation that culminate in the preeclampsia-like syndrome. Furthermore, the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a critical tumor suppressor, is markedly increased in the placentas of patients with preeclampsia. Our goal was to investigate the association of PTEN with preeclampsia and the pathways involved using human-trophoblast-derived cell line (HTR-8/SVneo) stimulated with LPS. We found that the expression of PTEN was significantly increased in the placentas of patients with severe preeclampsia and preeclamptic rat model induced by LPS. In vitro trophoblasts results showed that significantly differential expression of PTEN with corresponding changes in JunB/FosB (subunits of AP-1) and NF-κB activity after LPS stimulation. We further demonstrated that LPS-induced PTEN expression was dependent on AP-1 and NF-κB in trophoblasts. The trophoblasts with enforced expression of PTEN showed a reduced ability to invasion. Taken together, LPS may undermine remodelling of the human-trophoblast-derived HTR-8/SVneo cells by increasing PTEN, acting in part through the AP-1 and NF-κB pathways.

中文翻译：

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通过LPS / AP-1 /NF-κB途径上调PTEN会抑制滋养细胞入侵，从而导致先兆子痫。

子痫前期是一种妊娠特有的疾病，其特征在于滋养层浸润不足，导致螺旋动脉的血管重构异常。在怀孕第5天对怀孕大鼠施用脂多糖（LPS）可能会在母胎界面引起过度的免疫反应，导致早期胎盘发育不良，最终导致先兆子痫样综合征。此外，先兆子痫患者的胎盘中第10号染色体（PTEN）（一种重要的肿瘤抑制因子）上缺失的磷酸酶和张力蛋白同源物的表达显着增加。我们的目标是研究PTEN与子痫前期的关系以及使用LPS刺激的人滋养细胞衍生细胞系（HTR-8 / SVneo）所涉及的途径。我们发现，在患有严重子痫前期和LPS诱发的子痫前期大鼠模型的胎盘中，PTEN的表达显着增加。体外滋养细胞结果显示，LPS刺激后，PTEN的表达差异显着，JunB / FosB（AP-1的亚基）和NF-κB活性发生相应变化。我们进一步证明，LPS诱导的PTEN表达依赖于滋养细胞中的AP-1和NF-κB。PTEN表达增强的滋养细胞显示出降低的侵袭能力。总之，LPS可能通过增加PTEN（部分通过AP-1和NF-κB途径起作用）来破坏人滋养层细胞衍生的HTR-8 / SVneo细胞的重塑。体外滋养细胞结果显示，LPS刺激后，PTEN的表达差异显着，JunB / FosB（AP-1的亚基）和NF-κB活性发生相应变化。我们进一步证明，LPS诱导的PTEN表达依赖于滋养细胞中的AP-1和NF-κB。PTEN表达增强的滋养细胞显示出降低的侵袭能力。总之，LPS可能通过增加PTEN（部分通过AP-1和NF-κB途径起作用）来破坏人滋养层细胞衍生的HTR-8 / SVneo细胞的重塑。体外滋养细胞结果显示，LPS刺激后，PTEN的表达差异显着，JunB / FosB（AP-1的亚基）和NF-κB活性发生相应变化。我们进一步证明，LPS诱导的PTEN表达依赖于滋养细胞中的AP-1和NF-κB。PTEN表达增强的滋养细胞显示出降低的侵袭能力。总之，LPS可能通过增加PTEN（部分通过AP-1和NF-κB途径起作用）来破坏人滋养层细胞衍生的HTR-8 / SVneo细胞的重塑。