Yuanying He1, Li Chen2, Chunhong Liu3, Ying Han3, Chao Liang3, Qigui Xie4, Jianhong Zhou5, Zhongping Cheng6. 1. Department of Gynecology and Obstetrics, Shanghai Tenth People's Hospital, Tongji University School of Medicine, No. 301, Yanchangzhong Road, Shanghai 200072, China. Electronic address: haze19841224@me.com. 2. Department of Gynecology and Obstetrics, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, 2800 Gongwei Road, Pudong, Shanghai 201399, China. 3. Department of Gynecology and Obstetrics, Shanghai Tenth People's Hospital, Tongji University School of Medicine, No. 301, Yanchangzhong Road, Shanghai 200072, China. 4. Department of Gynecology and Obstetrics, Shanghai Tenth People's Hospital, Tongji University School of Medicine, No. 301, Yanchangzhong Road, Shanghai 200072, China. Electronic address: cykstar@163.com. 5. Department of Gynecology and Obstetrics, Shanghai Tenth People's Hospital, Tongji University School of Medicine, No. 301, Yanchangzhong Road, Shanghai 200072, China. Electronic address: zhoujoy0377@163.com. 6. Department of Gynecology and Obstetrics, Shanghai Tenth People's Hospital, Tongji University School of Medicine, No. 301, Yanchangzhong Road, Shanghai 200072, China. Electronic address: mdcheng18@263.net.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: The present study suggested that inhibition of the expression of STOX1 could promote the effects of aspirin in the treatment of preeclampsia.
BACKGROUND: 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. METHODS: The humanchoriocarcinoma 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. RESULTS: 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. CONCLUSION: The present study suggested that inhibition of the expression of STOX1 could promote the effects of aspirin in the treatment of preeclampsia.