Abstract | INTRODUCTION: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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.
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Authors | B Zhuang, X Luo, H Rao, Q Li, N Shan, X Liu, H Qi |
Journal | Placenta
(Placenta)
Vol. 36
Issue 8
Pg. 839-46
(Aug 2015)
ISSN: 1532-3102 [Electronic] Netherlands |
PMID | 26166436
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2015 Elsevier Ltd. All rights reserved. |
Chemical References |
- CCAAT-Enhancer-Binding Protein-beta
- Reactive Oxygen Species
- TIMP1 protein, human
- Tissue Inhibitor of Metalloproteinase-1
- beta Catenin
- Matrix Metalloproteinases
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Topics |
- CCAAT-Enhancer-Binding Protein-beta
(metabolism)
- Cell Line
- Female
- Humans
- Hypoxia
(metabolism)
- Matrix Metalloproteinases
(metabolism)
- Oxidative Stress
(physiology)
- Placenta
(metabolism)
- Placentation
(physiology)
- Pre-Eclampsia
(metabolism)
- Pregnancy
- Reactive Oxygen Species
(metabolism)
- Signal Transduction
(physiology)
- Tissue Inhibitor of Metalloproteinase-1
(metabolism)
- beta Catenin
(metabolism)
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