Vascular endothelial growth factor C participates in regulation of maspin in extravillous trophoblast cell migration and invasion
Xinwei Shi A , Guoqiang Zheng B , Hao Liu C , Jing Cao A , Wanlu Liu A , Yuqi Li A , Fuyuan Qiao A , Dongrui Deng A and Yuanyuan Wu
A D
+ Author Affiliations
- Author Affiliations
A Department of Obstetrics and Gynecology, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.
B Department of Obstetrics and Gynecology, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi 214023, Jiangsu, China.
C Department of Urology, Wuhan Third Hospital, Wuhan 430000, Hubei, China.
D Corresponding author. Email: qianmei98@163.com
Reproduction, Fertility and Development 31(8) 1410-1418 https://doi.org/10.1071/RD18438
Submitted: 29 October 2018 Accepted: 20 February 2019 Published: 30 April 2019
Abstract
Mammary serine protease inhibitor (maspin; also known as serpin family B member 5 (SERPINB5)) plays a vital role in regulating the biological functions of extravillous trophoblast (EVT) cells, but the mechanism remains unclear. Vascular endothelial growth factor (VEGF) C is a signature angiogenic molecule expressed and secreted by first-trimester trophoblasts, and bioinformatics analyses has revealed upregulation of VEGFC in pre-eclampsia. The aim of this study was to explore whether maspin regulates EVT cells by regulating the expression of VEGFC. Reverse transcription–polymerase chain reaction and western blotting were used to investigate the effects of hypoxia on the expression of VEGFC in EVT cells. Cells were treated with recombinant (r) maspin and decitabine (to selectively inhibit DNA methyltransferases and then upregulate maspin gene expression), and the effects on VEGFC expression evaluated. In addition, the effects of rVEGFC on the biological functions of EVT cells in vitro were evaluated using cell migration and invasion assays. Hypoxia increased the expression of VEGFC in EVT cells. rMaspin upregulated the expression of VEGFC in normoxic EVT cells, and downregulated the expression of VEGFC in hypoxic EVT cells at 24 h. Decitabine increased VEGFC expression in normoxic EVT cells, but had no significant effect on VEGFC expression in hypoxic EVT cells. rVEGFC promoted the migration and invasion of normoxic EVT cells and inhibited the invasion of hypoxic EVT cells. These results suggest that VEGFC is involved in the regulation of maspin in EVT cell migration and invasion. However, other molecular mechanisms may be involved and require further investigation.
Additional keywords: gene regulation, placenta, pre-eclampsia.
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