Oxidative stress-induced C/EBPβ inhibits β-catenin signaling molecule involving in the pathology of preeclampsia. Issue 8 (August 2015)

• Record Type: Journal Article
• Authors: Zhuang, B.; Luo, X.; Rao, H.; Li, Q.; Shan, N.; Liu, X.; Qi, H.
• Is Part Of: Placenta. Volume 36:Issue 8(2015:Aug.)
• Page Start: 839
• Page End: 846
• Publication Date: 2015-08
• Subjects: Placenta -- Periodicals; Reproduction -- Periodicals; Placenta -- Periodicals; Placenta -- Périodiques; Reproduction -- Périodiques; 612.63
• DOI: 10.1016/j.placenta.2015.06.016
• Languages: English
• ISSNs: 0143-4004

Abstract

<abstract xml:lang="en" abstract-type="author" id="abs0010"> <title id="sectitle0010">Abstract</title> <sec> <title id="sectitle0015">Introduction</title> <p id="abspara0010">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 placenta and to identify the underlying mechanisms of oxidative stress.</p> </sec> <sec> <title id="sectitle0020">Methods</title> <p id="abspara0015">Human placental tissues with PE were collected. The expression of C/EBPβ and β-catenin were detected. 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/EBPβ and β-catenin in placentation.</p> </sec> <sec> <title id="sectitle0025">Results</title> <p id="abspara0020">In preeclamptic placentas, C/EBPβ was overexpressed and β-catenin was decreased. In addition, C/EBPβ was found to have increased expression in H/R-treated HTR8/SVneo cells and villous explants. C/EBPβ knockdown and β-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.</p> </sec> <sec> <title id="sectitle0030">Discussion</title> <p id="abspara0025">We hypothesize that the oxidative stress-induced overexpression of C/EBPβ might influence the activity of MMPs by regulating the Wnt/β-catenin signaling pathway to affect the invasion of trophoblast cells, which then participate in the pathogenesis of preeclampsia.</p> </sec> </abstract>