Chemotactic properties of angiopoietin-1 and -2, ligands for the endothelial-specific receptor tyrosine kinase Tie2
Chemotactic properties of angiopoietin-1 and -2, ligands for the endothelial-specific receptor tyrosine kinase Tie2
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DOI：
10.1074/jbc.273.29.18514
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发表时间：
1998-07-17
影响因子：
4.8
通讯作者：
Isner, JM
中科院分区：
文献类型：
--
作者：
Witzenbichler, B;Maisonpierre, PC;Isner, JM
血管生成素-1及其假定的天然拮抗剂，血管生成素-2，最近被分离出来，和血管生成素-1在胚胎发生性血管生成的关键作用被证明了有针对性的基因破坏。然而，促血管生成素-1的具体生物学作用尚未确定。在这项研究中，我们证明了血管生成素-1，而不是血管生成素-2，对内皮细胞具有趋化性。相反，血管生成素-1以及血管生成素-2对内皮细胞没有增殖作用。过量的可溶性Tie 2，而不是蒂尔受体，取消内皮细胞对血管生成素-1的趋化反应。血管生成素-2剂量依赖性地阻止向血管生成素-1的定向迁移，这与血管生成素-2作为血管生成素-1天然抑制剂的作用一致。Tie 2受体稳定转染的成纤维细胞对血管生成素-1和血管生成素-2都表现出趋化反应。稳定表达由融合至Tie 2的胞质结构域的TrkC的胞外域组成的转染的嵌合受体的成纤维细胞也表现出对神经营养因子3（NT-3）（TrkC的特异性配体）的趋化反应。显示内皮细胞表达血管生成素-2 mRNA和蛋白，表明血管生成素/Tie 2的自分泌激活的潜力。最后，Tie 2和血管生成素-1在正常人动脉和静脉中表达的证明表明，血管生成素/Tie 2的作用可能超出胚胎血管生成，以维持成人脉管系统的完整性。
Angiopoietin-1 and its putative natural antagonist, angiopoietin-2, were recently isolated, and the critical role of angiopoietin-1 in embryogenic angiogenesis was demonstrated by targeted gene disruption. Specific biological effects of angiopoietin-1, however, have yet to be defined. in this study we demonstrate that angiopoietin-1, but not angiopoietin-2, is chemotactic for endothelial cells. In contrast, angiopoietin-1 as well as angiopoietin-2 exhibit no proliferative effect on endothelial cells. Excess soluble Tie2, but not Tiel receptor, abolish the chemotactic response of endothelial cells toward angiopoietin-1. Angiopoietin-2 dose-dependently blocks directed migration toward angiopoietin-1, consistent with the role of angiopoietin-2 as a naturally occurring inhibitor of angiopoietin-1. Fibroblasts stably transfected with Tie2 receptor exhibit chemotactic responses for both angiopoietin-1 and angiopoietin-2. Fibroblasts stably expressing a transfected chimeric receptor consisting of the ectodomain of TrkC fused to the cytoplasmic domain of Tie2 also exhibit a chemotactic response to neurotrophin 3 (NT-3), a specific Ligand for TrkC, Endothelial cells are shown to express angiopoietin-2 mRNA and protein, indicating the potential for autocrine activation of angiopoietin/Tie2, Finally, the demonstration that Tie2 as well as angiopoietin-1 are expressed in normal human arteries and veins suggests that the role of angiopoietin/Tie2 may extend beyond embryonic angiogenesis to maintaining integrity of the adult vasculature.