Hypoxia inducible factor 1 alpha regulates matrigel-induced endovascular differentiation under normoxia in a human extravillous trophoblast cell line
Hypoxia inducible factor 1 alpha regulates matrigel-induced endovascular differentiation under normoxia in a human extravillous trophoblast cell line
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DOI：
10.1016/j.placenta.2008.01.006
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发表时间：
2008-04-01
期刊：
影响因子：
3.8
通讯作者：
Wake, N.
中科院分区：
文献类型：
--
作者：
Fukushima, K.;Murata, M.;Wake, N.
绒毛外滋养层（EVT）细胞在血管生成过程中模仿内皮细胞，诱导螺旋动脉重塑，增加流向绒毛内空间的血流。我们先前已经表明，涉及血管内皮生长因子（VEGF）轴的信号是通过细胞外基质的整合素信号传导进行血管内分化所必需的：这是通过使用人EVT细胞系TCL 1完成的，其显示管形成特异性地回忆内皮细胞的形态学变化。为了进一步研究EVT中的血管内分化，我们研究了缺氧诱导因子（HIF）1A的作用，HIF 1A是HIF 1转录因子的一个亚基，不仅调节对缺氧的适应性反应，而且调节常氧下的许多细胞功能，在常氧下基质胶诱导的血管内分化过程中，HIF 1A在DNA微阵列分析中上调。HIF 1A诱导VEGF和ITGAV/ITGB 3聚集。已知对于EVT中的细胞存活和血管内分化非常重要的作用。使用siRNA引入或化学抑制抑制HIF 1A上调抑制缺氧反应元件转录活性、VEGF诱导、ITGAV/ITGB 3聚集，伴随着抑制TCL 1细胞中的管形成。这些结果表明，HIF 1A在调节EVT的行为，包括基质胶诱导的血管内分化在常氧下具有至关重要的作用。(C)2008爱思唯尔有限公司保留所有权利。
Extravillous trophoblast (EVT) cells mimic endothelial cells during angiogenesis, inducing remodeling of the spiral arteries that increases blood flow toward the intravillous space. We have previously shown that signals involving the vascular endothelial growth factor (VEGF) axis are essential for endovascular differentiation through integrin signaling from the extracellular matrix: This was accomplished with use of the human EVT cell line TCL1, which shows tube formation that specifically recalls morphological changes in endothelial cells. To investigate endovascular differentiation in EVT further, we investigated the role of hypoxia inducible factor (HIF)1A, a subunit of HIF1 transcription factor that regulates not only adaptive responses to hypoxia, but also many cellular functions under normoxia, which was up-regulated in DNA microarray analysis during matrigel-induced endovascular differentiation under normoxia. HIF1A induces VEGF and ITGAV/ITGB3 aggregation. actions known to be important for cellular survival and endovascular differentiation in EVT. Inhibition of HIF1A up-regulation using siRNA introduction or chemical inhibition suppressed hypoxia-responsive element transcriptional activity, VEGF induction, ITGAV/ITGB3 aggregation accompanied by the inhibition of tube formation in TCL1 cells. These results suggest that HIF1A has a crucial role in regulating EVT behavior including matrigel-induced endovascular differentiation under normoxia. (C) 2008 Elsevier Ltd. All rights reserved.