The role of SATB1 in HTR8/SVneo cells and pathological mechanism of preeclampsia

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 beta-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 beta-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/beta-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 beta-catenin and the migratory and invasive abilities of trophoblast. Conclusions: Our data suggested that oxidative stress reduced SATB1 leading to inhibition of Wnt/beta-catenin, and participate in the subdued migration and invasion of trophoblast, which indicated a potential pathological mechanism of PE.