SATB1 down-regulation induced by oxidative stress participates in trophoblast invasion by regulating β-catenin.

Preeclampsia (PE) is characterized by abnormal placentation in the early stages of pregnancy. Adequate migration and invasion of trophoblasts into the uterine wall and spiral arteries to form a functional maternal-fetal interface are pivotal for normal placentation, but the exact mechanism remains unclear. Growing evidence has revealed that special AT-rich sequence-binding protein 1 (SATB1) is a tumor promoter that participates in cancer cell migration and invasion. However, the expression and function of SATB1 in trophoblasts is unknown. Here, we characterize the stimulatory effect of SATB1 on the migration and invasion of trophoblasts and identify the regulatory events and downstream signaling components. Down-regulated SATB1 was detected in PE placentae and villous explants cultured under hypoxia/re-oxygenation (H/R) conditions. H/R-treated trophoblasts with lower SATB1 levels exhibited weaker invasive and growth capacities, whereas up-regulation of the SATB1 level with recombinant SATB1 restored these impairments. This restoration was especially apparent with the sumoylation-deficientSATB1 variant, which contained a mutated site that blocked sumoylation. Moreover, the elevated concentration of SATB1 also increased the expression of β-catenin, which is involved in human placental trophoblast invasion and differentiation and is down-regulated in PE. However, a specific activator, namely, lithium chloride (LiCl), increased β-catenin expression but had no evident influence on SATB1expression. Furthermore, up-regulated SATB1 failed to restore trophoblast function when Wnt/β-catenin was suppressed by Dickkopf1(DKK1).Together, these data show thatSATB1expression in the human placenta is affected by oxidative stress and might regulate the migration and invasion of trophoblasts via β-catenin signaling.