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Effects of Gadd45α-knockdown on human extravillous trophoblast cell migration and invasion functions under hypoxia/re-oxygenation

MU Hua-qiao1, LUO Xin2, QI Hong-bo2, LIU Xi-ru2   

  1. 1. Medical Department, Chongqing Health Centre for Women and Children, Chongqing 400013, China; 2. Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
  • Online:2017-03-28 Published:2017-03-30
  • Supported by:

    National Natural Science Foundation of China, 81300508


Objective · To investigate the effects of growth arrest and DNA damage 45 alpha (Gadd45α) on the migration and invasion function of human extravillous trophoblast cells under hypoxia/re-oxygenation (H/R). Methods · Human extravillous trophoblast cells were infected by shRNA lentivirus targeting Gadd45α gene, to knock down Gadd45α gene expression. Then the oxidative stress model of preeclampsia was used in vitro to observe the changes of cell biological functions. The experiments were divided into 4 groups, nontreated group, hypoxia/re-oxygenation group, shRNA Gadd45α+H/R group and shRNA negative control+H/R group. Human villous explant experiments were used to determine the effects of silencing Gadd45α on human extravillous trophoblast cell under oxidative stress. Protein expression of Gadd45α was identified by Western blotting. Changes of cell migration and invasion were detected by transwell migration and Matrigel invasion assay. Gelatin zymography was used to detect the expression of matrix metalloproteinase (MMP) -2/9 in culture medium. Results · Hypoxia/re-oxygenation can increase the expression of Gadd45α in HTR8/SVneo cells and damage the trophoblast cell migration and invasion. Knocking down Gadd45α can increase the activities of MMP2/9, which can increase the cell migration and invasion. Conclusion · Knockdown of Gadd45α gene has promoted cell migration and invasion function of human extravillous trophobalst cells under oxidative stress.

Key words: growth arrest and DNA damage 45 alpha, human extravillous trophoblast cells, oxidative stress