Department of Gynecology and Obstetrics, Shanghai Tenth People's Hospital, Tongji University School of Medicine, No. 301, Yanchangzhong Road, Shanghai 200072, China.
Department of Gynecology and Obstetrics, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, 2800 Gongwei Road, Pudong, Shanghai 201399, China.
Pregnancy Hypertens. 2020 Jan;19:170-176. doi: 10.1016/j.preghy.2019.12.011. Epub 2020 Jan 17.
A major cause of preeclampsia is the placental ischemia caused by insufficient trophoblast cells, invading into the spiral artery. Storkhead-box protein 1 (STOX1) is highly associated with preeclampsia. Meanwhile, low-dose aspirin for patients with preeclampsia is effective in reducing the incidence of preeclampsia. The aim of the present study was to explore the underlying mechanism, and the relationship between STOX1 and aspirin in preeclampsia.
The human choriocarcinoma cell line JEG-3 was employed to mimic trophoblast cells and establish a model for trophoblast cells overexpressing STOX1 and knockdown of JEG cell lines, which were treated with aspirin afterwards. Cell counting kit-8 (CCK-8) assay was utilized to estimate cell proliferation and optimal concentration of aspirin for further experiments. Meanwhile, transwell assay was used to detect migration, and flow cytometry was used to measure apoptosis. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blotting were applied to analyze the expression levels of STOX1 and related genes.
Overexpression of STOX1 inhibited proliferation of JEG-3 cells through epidermal growth factor (EGF), vascular EGF (VEGF), and transforming growth factor beta 1 (TGF-β1) proteins, while suppressed migration through MMP2, MMP9, and E-cadherin proteins. In contrast, apoptosis of JEG-3 cells was elevated by STOX1 through Bcl-2, Bax, and Cox-2 proteins. Furthermore, we found that aspirin modulated the expression level of STOX1 and reversed proliferation and migration of STOX1-induced insufficient trophoblast cells.
The present study suggested that inhibition of the expression of STOX1 could promote the effects of aspirin in the treatment of preeclampsia.
子痫前期的一个主要原因是由于滋养细胞不足，侵入螺旋动脉，导致胎盘缺血。Storkhead-box 蛋白 1（STOX1）与子痫前期高度相关。同时，低剂量阿司匹林可有效降低子痫前期患者的子痫前期发病率。本研究旨在探讨 STOX1 与阿司匹林在子痫前期中的潜在作用机制及关系。
采用人绒毛膜癌细胞系 JEG-3 模拟滋养细胞，建立 STOX1 过表达和 JEG 细胞系敲低模型，然后用阿司匹林处理。细胞计数试剂盒-8（CCK-8）检测细胞增殖，确定阿司匹林的最佳浓度用于进一步实验。Transwell 检测细胞迁移，流式细胞术检测细胞凋亡。实时定量聚合酶链反应（RT-qPCR）和 Western blot 分析 STOX1 及相关基因的表达水平。
STOX1 过表达通过表皮生长因子（EGF）、血管内皮生长因子（VEGF）和转化生长因子-β1（TGF-β1）蛋白抑制 JEG-3 细胞增殖，通过 MMP2、MMP9 和 E-cadherin 蛋白抑制迁移。相反，STOX1 通过 Bcl-2、Bax 和 Cox-2 蛋白促进 JEG-3 细胞凋亡。此外，我们发现阿司匹林调节 STOX1 的表达水平，并逆转 STOX1 诱导的滋养细胞不足的增殖和迁移。
本研究表明抑制 STOX1 的表达可增强阿司匹林治疗子痫前期的效果。
