Vascular endothelial growth factor C participates in regulation of maspin in extravillous trophoblast cell migration and invasion
Vascular endothelial growth factor C participates in regulation of maspin in extravillous trophoblast cell migration and invasion
复制标题
血管内皮生长因子C参与maspin对绒毛外滋养层细胞迁移和侵袭的调节
DOI：
10.1071/rd18438
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Wu Yuanyuan
中科院分区：
文献类型：
--
作者：
Shi Xinwei;Zheng Guoqiang;Liu Hao;Cao Jing;Liu Wanlu;Li Yuqi;Qiao Fuyuan;Deng Dongrui;Wu Yuanyuan
乳腺丝氨酸蛋白酶抑制因子(Maspin，又称丝氨酸蛋白B家族成员5，SERPINB5)在调节绒毛外滋养细胞(EVT)的生物学功能中起重要作用，但其作用机制尚不清楚。血管内皮生长因子(VEGF)C是妊娠早期滋养层细胞表达和分泌的标志性血管生成分子，生物信息学分析显示VEGFC在子痫前期表达上调。本研究的目的是探讨maspin是否通过调节VEGFC的表达来调节EVT细胞。采用逆转录聚合酶链式反应和免疫印迹法检测缺氧对EVT细胞VEGFC表达的影响。用重组(R)maspin和地西他滨(选择性抑制DNA甲基转移酶，进而上调maspin基因表达)处理细胞，评价其对VEGFC表达的影响。此外，通过细胞迁移和侵袭实验评价了重组VEGFC对 细胞生物学功能的影响。低氧使EVT细胞VEGFC表达增加。RMaspin上调常氧血管内皮细胞VEGFc的表达，下调缺氧血管内皮细胞VEGFc的表达，地西他滨可上调常氧血管内皮细胞VEGFc的表达，但对缺氧性血管内皮细胞VEGFc的表达无明显影响。RVEGFC促进常氧EVT细胞的迁移和侵袭，抑制低氧EVT细胞的侵袭。这些结果提示VEGFC参与了maspin在EVT细胞迁移和侵袭中的调控。然而，可能涉及其他分子机制，需要进一步研究。
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.