The role of SATB1 in HTR8/SVneo cells and pathological mechanism of preeclampsia.
The role of SATB1 in HTR8/SVneo cells and pathological mechanism of preeclampsia.
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SATB1在HTR8/SVneo细胞中的作用及子痫前期的病理机制
DOI：
10.1080/14767058.2018.1425387
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发表时间：
2018
影响因子：
1.8
通讯作者：
Qi H
中科院分区：
文献类型：
--
作者：
Rao H;Bai Y;Zhang F;Li Q;Zhuang B;Luo X;Qi H
摘要目的：特异性富含AT序列结合蛋白1（SATB 1）在肿瘤细胞的侵袭和转移中发挥重要作用，并参与胎盘和胎儿的发育。本研究旨在探讨SATB 1在滋养细胞迁移和侵袭中的作用及其可能机制。研究方法：方法：采用免疫组织化学方法检测SATB 1和β-catenin在早孕、中孕、足月及子痫前期（PE）胎盘组织中的表达及亚细胞定位。采用缺氧/复氧（H/R）、氯化锂（LiCl）或SATB 1-siRNA处理人滋养层细胞系HTR 8/SVneo，研究SATB 1和β-catenin信号通路在人滋养层细胞功能中的作用。结果：SATB 1在胎盘组织中特异性定位于滋养层细胞。SATB 1在妊娠过程中表达逐渐降低，PE患者胎盘组织中SATB 1的表达较正常妊娠组明显降低。此外，SATB 1在H/R处理的HTR 8/Svneo细胞和绒毛外植体中的表达降低。Wnt/β-catenin信号通路与SATB 1表达相互作用，H/R处理导致滋养细胞Wnt通路抑制，而氯化锂（LiCl）处理增强H/R暴露的HTR 8/SVneo迁移和侵袭。SATB 1基因敲低可显著降低β-catenin水平及滋养细胞的迁移和侵袭能力。结论：提示氧化应激导致SATB 1表达减少，Wnt/β-catenin表达受到抑制，参与滋养细胞迁移和侵袭，可能是PE的一个潜在病理机制。
Abstract Objective: 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. Methods: 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. Results: 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. Conclusions: 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.