β-TrCP suppresses the migration and invasion of trophoblast cells in preeclampsia by down-regulating Snail

Abstract

Insufficient trophoblast invasion has been shown to contribute to the occurrence and progression of preeclampsia (PE). Recently, beta-transducin repeat containing E3 ubiquitin protein (β-TrCP) was shown to function as a ubiquitination regulator in regulating the proliferation and invasion of various cell types. In this study, we employed an in vitro model of trophoblasts to investigate the role played by β-TrCP in the pathogenesis of PE. The levels of β-TrCP in newly delivered placentas from 15 pregnant women with PE and 15 healthy pregnant women were detected by quantitative real-time PCR and western blot assays. The effects of β-TrCP on cell migration, invasion, and epithelial-mesenchymal transition (EMT) in two trophoblast cell lines (HTR-8/SVneo and TEV-1) were examined using wound healing assays, Transwell assays, and western blot assays, respectively. Rescue experiments were performed by treating β-TrCP knockdown or β-TrCP expressing trophoblasts with si-Snail transfection or a proteasome inhibitor (MG132). β-TrCP mRNA and protein expression levels were significantly increased in the PE placentas when compared to the normal control placentas. β-TrCP overexpression significantly inhibited cell migration and invasion, while silencing of β-TrCP promoted cell migration and invasion of the two trophoblast cell lines. Furthermore, we demonstrated that β-TrCP-mediated ubiquitination might inhibit the EMT process of trophoblasts by down-regulating Snail expression. Our results suggest that both β-TrCP mRNA and protein expression were up-regulated in the PE placentas. β-TrCP impeded the migration and invasion of trophoblasts by suppressing Snail expression. This implicates the ubiquitin-proteasome pathway in the pathogenesis of PE, and suggests β-TrCP as a potential target for treating PE.