title: Oxidative stress-induced C/EBPβ inhibits β-catenin signaling molecule involving in the pathology of preeclampsia.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Yixue Road, Yuzhong District, Chongqing 400016, China.
authors.forename: B
authors.initials: B
authors.lastname: Zhuang
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Yixue Road, Yuzhong District, Chongqing 400016, China.
authors.forename: X
authors.initials: X
authors.lastname: Luo
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Yixue Road, Yuzhong District, Chongqing 400016, China.
authors.forename: H
authors.initials: H
authors.lastname: Rao
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Yixue Road, Yuzhong District, Chongqing 400016, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Yixue Road, Yuzhong District, Chongqing 400016, China.
authors.forename: N
authors.initials: N
authors.lastname: Shan
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Yixue Road, Yuzhong District, Chongqing 400016, China.
authors.forename: X
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Yixue Road, Yuzhong District, Chongqing 400016, China. Electronic address: qihongbo@sina.com.
authors.forename: H
authors.initials: H
authors.lastname: Qi
mesh_terms: D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism*; D002460:Cell Line; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D010920:Placenta / Q000378:metabolism; D010929:Placentation / Q000502:physiology; D011225:Pre-Eclampsia / Q000378:metabolism*; D011247:Pregnancy; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D017382:Reactive Oxygen Species; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D051176:beta Catenin; D020782:Matrix Metalloproteinases
keywords: CCAAT/enhancer binding protein beta (C/EBPβ); First trimester-derived placental villous explant; Oxidative stress; Preeclampsia; Trophoblast; β-catenin