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13 March 2018 SATB1 downregulation induced by oxidative stress participates in trophoblast invasion by regulating β-catenin
Haiying Rao, Yuxiang Bai, Qingshu Li, Baimei Zhuang, Yu Yuan, Yamin Liu, Wei Peng, Philip N. Baker, Chao Tong, Xin Luo, Hongbo Qi
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Abstract

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 (binds to nuclear matrix/scaffold-associating DNA) (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. Downregulated SATB1 was detected in PE placentae and villous explants cultured under hypoxia/reoxygenation (H/R) conditions. H/R-treated trophoblasts with lower SATB1 levels exhibited weaker invasive and growth capacities, whereas upregulation of the SATB1 level with recombinant SATB1 restored these impairments. This restoration was especially apparent with the sumoylation-deficient SATB1 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 is downregulated in PE. However, a specific activator, namely, lithium chloride (LiCl), increased β-catenin expression but had no evident influence on SATB1 expression. Furthermore, upregulated SATB1 failed to restore trophoblast function when Wnt/β-catenin was suppressed by dickkopf (Xenopus laevis) homolog 1, dickkopf 1 homolog (Xenopus laevis) (DKK1). Together, these data show that SATB1expression in the human placenta is affected by oxidative stress and might regulate the migration and invasion of trophoblasts via β-catenin signaling.

© The Author(s) 2018. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com
Haiying Rao, Yuxiang Bai, Qingshu Li, Baimei Zhuang, Yu Yuan, Yamin Liu, Wei Peng, Philip N. Baker, Chao Tong, Xin Luo, and Hongbo Qi "SATB1 downregulation induced by oxidative stress participates in trophoblast invasion by regulating β-catenin ," Biology of Reproduction 98(6), 810-820, (13 March 2018). https://doi.org/10.1093/biolre/ioy033
Received: 4 August 2017; Accepted: 8 March 2018; Published: 13 March 2018
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