Oxidative Stress-Induced C/EBPβ Inhibits β-Catenin Signaling Molecule Involving In The Pathology Of Preeclampsia

Objective:Oxidative stress-induced trophoblast cell dysfunction is a major pathology in preeclampsia (PE). Recently, CCAAT/enhancer binding protein beta (C/EBPβ) has been investigated as a tumor suppressor that participates in tumor invasion. However, the function of C/EBPβ in trophoblast cells remains unknown. Our study was designed to detect the expression of C/EBPβ in the preeclamptic human placenta and to identify the underlying mechanisms of oxidative stress.Methods:Human placental tissues with PE were collected. And the expression of C/EBPβ and P-catenin were detected. The human first trimester extravillous trophoblast cell (HTR8/SVneo) line exposed to hypoxia/reoxygenation(H/R) was employed as an oxidative stress model in vitro to investigate the effects of C/EBPβ on invasion and the expression of β-catenin. Moreover, first trimester-derived placental villous explants were used to verify the effects of C/EBPP and β-catenin in placentation.Results:C/EBPβ was overexpressed in preeclamptic placentas and β-catenin was decreased in placentas with PE. In addition, C/EBPP was found to have increased expression in H/R-treated HTR8/SVneo cells and villous explants. C/EBPβ knockdown and P-catenin activation could significantly promote the invasion of HTR8/SVneo cells, enhance the outgrowth and migration in villous explants and inhibit the excessive generation of intracellular ROS. These findings might be related to the increased activities of MMP-2/9 and the decreased expression of TIMP-1/2. Meanwhile, C/EBPβ knockdown remarkably increased the expression of β-catenin.Conclusion:We hypothesize that the oxidative stress-induced overexpression of C/EBPβ might influence the activity of MMPs by regulating the Wnt/p-catenin signalig pathway to affect the invasion of trophoblast cells, which then participate in the pathogenesis of preeclampsia.