Placental trophoblast apoptosis is a major pathological feature of preeclampsia. Fas has been reported to be highly expressed in the placentas of patients with preeclampsia. However, the role and underlying mechanisms of Fas in the pathogenesis of preeclampsia have not been elucidated. In the present study, the expression of Fas in JAR human choriocarcinoma cells was overexpressed and knocked down to determine the function and possible mechanism of Fas in trophoblast cells in the progression of preeclampsia. The results of flow cytometry, Cell Counting Kit-8 and Transwell assays indicated that the overexpression of Fas promoted apoptosis, suppressed viability and impaired the migration of the human trophoblast cells. In addition, western blotting revealed that the overexpression of Fas increased the expression of nuclear factor kB (NF-kB), Bax, tumor necrosis factor α (TNF-α) and interleukin-2 (IL-2), and decreased the expression of Bcl-2 at the protein level in trophoblast cells. By contrast, the knockdown of Fas decreased the apoptosis of trophoblast cells and increased their viability and migration. In addition, the knockdown of Fas suppressed the expression of NF-κB, Bax, TNF-α and IL-2, and increased the expression of Bcl-2. Notably, the overexpression of NF-κB p65 attenuated the Fas knockdown-induced inhibition of apoptosis and acceleration of migration of the trophoblast cells. The overexpression of NF-κB in trophoblast cells also reversed the reduction in Bax expression and increase in Bcl-2 expression induced by Fas knockdown in trophoblast cells. These results indicate that Fas regulates the apoptosis and migration of trophoblast cells by targeting NF-κB, which suggests that the silencing of Fas is a promising therapeutic strategy for preeclampsia.

中文翻译：

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Fas 通过靶向 NF-κB 调节滋养层细胞的凋亡和迁移。

胎盘滋养细胞凋亡是先兆子痫的主要病理特征。据报道，Fas 在先兆子痫患者的胎盘中高度表达。然而，Fas 在先兆子痫发病机制中的作用和潜在机制尚未阐明。在本研究中，JAR 人绒毛膜癌细胞中 Fas 的表达被过表达和敲低，以确定 Fas 在先兆子痫进展中滋养层细胞中的功能和可能机制。流式细胞术、Cell Counting Kit-8 和 Transwell 检测的结果表明，Fas 的过表达促进了细胞凋亡，抑制了人滋养层细胞的活力并损害了其迁移。此外，蛋白质印迹显示 Fas 的过表达增加了核因子 kB (NF-kB)、Bax、肿瘤坏死因子α (TNF-α) 和白细胞介素-2 (IL-2)，并在滋养层细胞的蛋白质水平上降低 Bcl-2 的表达。相比之下，Fas 的敲低减少了滋养层细胞的凋亡并增加了它们的活力和迁移。此外，Fas 的敲低抑制了 NF-κB、Bax、TNF-α 和 IL-2 的表达，并增加了 Bcl-2 的表达。值得注意的是，NF-κB p65 的过表达减弱了 Fas 敲低诱导的细胞凋亡抑制和滋养层细胞迁移的加速。滋养层细胞中NF-κB的过表达也逆转了滋养层细胞中Fas敲低诱导的Bax表达的降低和Bcl-2表达的增加。这些结果表明 Fas 通过靶向 NF-κB 调节滋养层细胞的凋亡和迁移，