Plasma fibronectin 1 (FN1) levels are elevated in individuals with pre-eclampsia (PE), which may be applied as a possible biochemical marker for vascular endothelial injury during PE. In the present study, the possible role of FN1 in the pathogenesis of PE and regulation of apoptosis and autophagy in vascular endothelial cells was explored. Plasma FN1 levels in 80 patients with PE and 40 healthy pregnant individuals were measured using ELISA to verify its relationship with the severity of PE. pcDNA3.1-FN1 or FN1-small interfering (si) RNA was used to manipulate the expression of FN1 in human umbilical vein endothelial cells (HUVECs) to assess the effects of FN1 on cell apoptosis, autophagy and the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) signaling pathway. It was found that upregulation of FN1 promoted apoptosis and autophagy, in addition to significantly inhibiting the activation of AKT and mTOR in HUVECs. By contrast, downregulation of FN1 expression inhibited cell apoptosis and autophagy, but increased AKT and mTOR phosphorylation in HUVECs that were cultured in serum samples obtained from patients with PE. Rescue experiments found that the PI3K/AKT inhibitor LY294002 reversed the effects of FN1-siRNA on apoptosis and autophagy in HUVECs cultured in serum from patients with PE. Therefore, data from the present study suggest that FN1 participates in the pathogenesis of PE by promoting apoptosis and autophagy in vascular endothelial cells, which is associated with the PI3K/AKT/mTOR signaling pathway.

中文翻译：

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过量的纤连蛋白1通过促进血管内皮细胞的凋亡和自噬而参与先兆子痫的发病机理。

子痫前期（PE）患者的血浆纤连蛋白1（FN1）水平升高，可能被用作PE期间血管内皮损伤的可能的生化指标。在本研究中，探讨了FN1在PE的发病机理以及血管内皮细胞凋亡和自噬调控中的可能作用。使用ELISA测定了80例PE患者和40例健康孕妇的血浆FN1水平，以验证其与PE严重程度的关系。pcDNA3.1-FN1或FN1小干扰（si）RNA被用于操纵FN1在人脐静脉内皮细胞（HUVEC）中的表达，以评估FN1对细胞凋亡，自噬和磷酸肌醇3激酶（PI3K）的影响）/蛋白激酶B（AKT）/雷帕霉素（mTOR）信号传导途径的机械靶标。发现FN1的上调除了显着抑制HUVEC中AKT和mTOR的活化外，还促进细胞凋亡和自噬。相比之下，FN1表达的下调抑制了细胞凋亡和自噬，但增加了从PE患者血清样品中培养的HUVEC中的AKT和mTOR磷酸化。救援实验发现，PI3K / AKT抑制剂LY294002逆转了FN1-siRNA对PE患者血清中培养的HUVEC细胞凋亡和自噬的作用。因此，来自本研究的数据表明，FN1通过促进血管内皮细胞的凋亡和自噬来参与PE的发病机制，这与PI3K / AKT / mTOR信号通路相关。除了显着抑制HUVEC中AKT和mTOR的活化外。相比之下，FN1表达的下调抑制了细胞凋亡和自噬，但增加了从PE患者血清样品中培养的HUVEC中的AKT和mTOR磷酸化。救援实验发现，PI3K / AKT抑制剂LY294002逆转了FN1-siRNA对PE患者血清中培养的HUVEC细胞凋亡和自噬的作用。因此，来自本研究的数据表明，FN1通过促进血管内皮细胞的凋亡和自噬来参与PE的发病机制，这与PI3K / AKT / mTOR信号通路相关。除了显着抑制HUVEC中AKT和mTOR的活化外。相比之下，FN1表达的下调抑制了细胞凋亡和自噬，但增加了从PE患者血清样品中培养的HUVEC中的AKT和mTOR磷酸化。救援实验发现，PI3K / AKT抑制剂LY294002逆转了FN1-siRNA对PE患者血清中培养的HUVEC细胞凋亡和自噬的作用。因此，来自本研究的数据表明，FN1通过促进血管内皮细胞的凋亡和自噬来参与PE的发病机制，这与PI3K / AKT / mTOR信号通路相关。但在从PE患者获得的血清样本中培养的HUVEC中，AKT和mTOR磷酸化增加。救援实验发现，PI3K / AKT抑制剂LY294002逆转了FN1-siRNA对PE患者血清中培养的HUVEC细胞凋亡和自噬的作用。因此，来自本研究的数据表明，FN1通过促进血管内皮细胞的凋亡和自噬来参与PE的发病机制，这与PI3K / AKT / mTOR信号通路相关。但在从PE患者获得的血清样本中培养的HUVEC中，AKT和mTOR磷酸化增加。救援实验发现，PI3K / AKT抑制剂LY294002逆转了FN1-siRNA对PE患者血清中培养的HUVEC细胞凋亡和自噬的作用。因此，本研究的数据表明，FN1通过促进血管内皮细胞的凋亡和自噬来参与PE的发病机制，这与PI3K / AKT / mTOR信号通路相关。