Rao Haiying, Bai Yuxiang, Zhang Fumei, Li Qingshu, Zhuang Baimei, Luo Xin, Qi Hongbo
a Department of Obstetrics and Gynecology , the First Affiliated Hospital of Chongqing Medical University , Chongqing , China.
b China-Canada-New Zealand Joint Laboratory of Maternal and Fetal Medicine , Chongqing Medical University , Chongqing , China.
J Matern Fetal Neonatal Med. 2019 Jun;32(12):2069-2078. doi: 10.1080/14767058.2018.1425387. Epub 2018 Jan 16.
Special AT-rich sequence binding protein 1 (SATB1) play potential roles in invasion and metastasis of tumor cells, and involves in human placental and fetal development. The objective of this study is to explore the role of SATB1 in migration and invasion of trophoblast and the potential mechanism.
Human placental tissues from first trimester, second trimester, term, and preeclampsia (PE) pregnancies were used to detect the expression and subcellular location of SATB1 and β-catenin. The human trophoblast cell line HTR8/SVneo, which was treated with hypoxia/re-oxygenation (H/R), lithium chloride (LiCl) or SATB1-siRNA to investigate the role of SATB1 and β-catenin signaling in human trophoblast function.
We observed that SATB1 specifically localized within trophoblast cells of placenta tissues. Gradually reduced expression of SATB1 was observed during gestation, and lower expression were detected in placenta of PE compared with normal pregnancy. Moreover, the expression of SATB1 was decreased in H/R-treated HTR8/Svneo cells and villous explants. The Wnt/β-catenin signaling pathway interacted with SATB1 expression and H/R treatment resulted in Wnt pathway inhibition in trophoblast, while lithium chloride (LiCl) treatment enhanced H/R-exposed HTR8/SVneo migration and invasion. Knockdown of SATB1 significantly reduced the level of β-catenin and the migratory and invasive abilities of trophoblast.
Our data suggested that oxidative stress reduced SATB1 leading to inhibition of Wnt/β-catenin, and participate in the subdued migration and invasion of trophoblast, which indicated a potential pathological mechanism of PE.
富含AT序列结合蛋白1(SATB1)在肿瘤细胞侵袭和转移中发挥潜在作用,并参与人类胎盘和胎儿发育。本研究旨在探讨SATB1在滋养细胞迁移和侵袭中的作用及其潜在机制。
采用来自孕早期、孕中期、足月妊娠及子痫前期(PE)孕妇的人胎盘组织,检测SATB1和β-连环蛋白的表达及亚细胞定位。用人滋养细胞系HTR8/SVneo,分别给予缺氧/复氧(H/R)、氯化锂(LiCl)或SATB1-siRNA处理,以研究SATB1和β-连环蛋白信号通路在人滋养细胞功能中的作用。
我们观察到SATB1特异性定位于胎盘组织的滋养细胞内。在妊娠期间观察到SATB1表达逐渐降低,与正常妊娠相比,PE胎盘组织中SATB1表达更低。此外,H/R处理的HTR8/Svneo细胞和绒毛外植体中SATB1表达降低。Wnt/β-连环蛋白信号通路与SATB1表达相互作用,H/R处理导致滋养细胞中Wnt通路受到抑制,而氯化锂(LiCl)处理增强了H/R处理的HTR8/SVneo细胞的迁移和侵袭能力。敲低SATB1可显著降低β-连环蛋白水平以及滋养细胞的迁移和侵袭能力。
我们的数据表明,氧化应激降低SATB1导致Wnt/β-连环蛋白受到抑制,并参与滋养细胞迁移和侵袭能力的减弱,这提示了PE潜在的病理机制。