Impact of Hey2 and COUP-TFII on genes involved in arteriovenous differentiation in primary human arterial and venous endothelial cells
Impact of Hey2 and COUP-TFII on genes involved in arteriovenous differentiation in primary human arterial and venous endothelial cells
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DOI：
10.1007/s00395-013-0362-0
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发表时间：
2013-07-01
影响因子：
9.5
通讯作者：
Goettsch, Winfried
中科院分区：
文献类型：
--
作者：
Korten, Slobodanka;Brunssen, Coy;Goettsch, Winfried
动脉和静脉在解剖、生理和基因表达模式上存在显著差异。在本研究中，我们分析了人静脉和动脉内皮细胞中动脉标记基因Hey2和静脉标记基因COUP-TFII过表达或下调对动静脉分化相关基因的影响。慢病毒在动脉内皮细胞中过表达静脉标记基因COUP-TFII导致NICD4、动脉标记基因Hey2和EphrinB2下调。ChIP、EMSA和启动子分析表明，COUP-TFII可通过直接结合Hey2启动子介导Hey2的下调。shRNA下调Hey2导致EphrinB2表达下调。静脉内皮细胞中动脉标志物Hey2的过表达并未改变COUP-TFII的表达模式。静脉内皮细胞中静脉标记基因COUP-TFII下调导致VEGF-A、Dll4、EphrinB2表达上调。我们的数据支持Hey2和COUP-TFII在人内皮细胞动静脉分化中的重要作用。
Arteries and veins show marked differences in their anatomy, physiology and genetic expression pattern. In this study, we analyzed impact of overexpression or downregulation of arterial marker gene Hey2 and venous marker gene COUP-TFII in human venous and arterial endothelial cells on genes involved in arteriovenous differentiation. Lentiviral overexpression of venous marker gene COUP-TFII in arterial endothelial cells led to downregulation of NICD4, arterial marker gene Hey2 and EphrinB2. Downregulation of Hey2 could be mediated by direct binding of COUP-TFII to Hey2 promoter as shown by ChIP, EMSA and promoter analysis. Downregulation of Hey2 by shRNA causes downregulation of EphrinB2 expression. Overexpression of arterial marker Hey2 in venous endothelial cells did not change expression pattern of COUP-TFII. Downregulation of venous marker gene COUP-TFII in venous endothelial cells resulted in upregulation of VEGF-A, Dll4 and EphrinB2 expression. Our data support an important role of Hey2 and COUP-TFII in arteriovenous differentiation of human endothelial cells.