Gene regulation of a novel angiogenesis inhibitor, vasohibin, in endothelial cells
Gene regulation of a novel angiogenesis inhibitor, vasohibin, in endothelial cells
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DOI：
10.1016/j.bbrc.2004.12.073
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发表时间：
2005-02-18
影响因子：
3.1
通讯作者：
Sato, Y
中科院分区：
文献类型：
--
作者：
Shimizu, K;Watanabe, K;Sato, Y
我们最近报道，血管抑制素是血管生成的负反馈调节因子，并且它特异性地表达于内皮细胞。在这里，我们的特点的调节血管收缩素的表达。发现了两种可能的剪接变体，并且较长的同种型优先表达。VEGF诱导vasohibin的表达，并且这种诱导被抗VEGFR2 mAb而不是被抗VEGFR1 mAb废除。药理学分析表明，VEGFR2的下游靶点是PKC，尤其是PKC δ。放线菌素D没有改变VEGF处理后的血管收缩素mRNA诱导的动力学，而放线菌酮完全取消其诱导。我们检测了各种炎症细胞因子对血管收缩素表达的影响。TNF α、IL 1和IFN γ降低VEGF刺激的血管抑制素表达。放线菌素D并没有改变TNF α处理后血管收缩素mRNA诱导的动力学。这些结果表明，血管收缩素在内皮细胞中的表达在转录水平上受到某些因子的正或负调控。(C)2004年爱思唯尔公司All rights reserved.
We recently reported that vasohibin is a negative feedback regulator of angiogenesis, and it is specifically expressed in endothelial cells. Here, we characterize the regulation of vasohibin expression. Two possible splicing variants were found, and the longer isoform was preferentially expressed. VEGF induced the expression of vasohibin, and this induction was abrogated by anti-VEGFR2 mAb but not by anti-VEGFR1 mAb. Pharmacological analysis revealed that the downstream targets of VEGFR2 were PKCs, especially PKCdelta. Actinomycin D did not alter the kinetics of vasohibin mRNA induction upon VEGF treatment, whereas cycloheximide completely abolished its induction. We tested the effect of various inflammatory cytokines on vasohibin expression. TNFalpha, IL1, and IFNgamma decreased VEGF-stimulated vasohibin expression. Actinomycin D did not alter the kinetics of vasohibin mRNA induction upon TNFalpha treatment. These results indicate that the expression of vasohibin in endothelial cells is regulated either positively or negatively by certain factors at the transcriptional level. (C) 2004 Elsevier Inc. All rights reserved.