Angiopoietin-1 promotes LYVE-1-positive lymphatic vessel formation
Angiopoietin-1 promotes LYVE-1-positive lymphatic vessel formation
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DOI：
10.1182/blood-2004-08-3382
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发表时间：
2005-06-15
期刊：
影响因子：
20.3
通讯作者：
Suda, T
中科院分区：
文献类型：
--
作者：
Morisada, T;Oike, Y;Suda, T
血管生成素（Angiopoietin, Ang）信号通过受体酪氨酸激酶Tie2在血管内皮细胞（BECs）上表达，在血管新生和血管重塑中发挥作用。最近有研究表明，Ang-2对淋巴血管的形成至关重要，并且在Ang-2突变小鼠中发现的淋巴管生成缺陷可以通过Ang-1修复。这些发现提示了Ang信号在淋巴管系统中的重要作用；然而，Ang在淋巴管生成中的功能尚未明确。在这项研究中，我们发现淋巴血管内皮透明质酸受体1阳性（LYVE-1(+)）淋巴内皮细胞（LECs）在胚胎和成人环境中表达Tie2，表明Ang信号在淋巴管中发生。因此，我们研究了Ang-1是否对体内淋巴血管生成和LECs体外生长起作用。一种嵌合形式的Ang-1，软骨寡聚基质蛋白(COMP)-Ang-1，促进小鼠角膜体内淋巴血管生成。此外，我们发现COMP-Ang-1刺激LECs的体外集落形成。这些Ang-1诱导的体内和体外对LECs的影响被可溶性Tie2-Fc融合蛋白抑制，该蛋白通过隔离Ang-1起到抑制剂的作用。基于这些观察结果，我们提出Ang信号通过Tie2调节淋巴管形成。(c) 2005年由美国血液学会出版。
Angiopoietin (Ang) signaling plays a role in angiogenesis and remodeling of blood vessels through the receptor tyrosine kinase Tie2, which is expressed on blood vessel endothelial cells (BECs). Recently it has been shown that Ang-2 is crucial for the formation of lymphatic vasculature and that defects in lymphangiogenesis seen in Ang-2 mutant mice are rescued by Ang-1. These findings suggest important roles for Ang signaling in the lymphatic vessel system; however, Ang function in lymphangiogenesis has not been characterized. In this study, we reveal that lymphatic vascular endothelial hyaluronan receptor 1-positive (LYVE-1(+)) lymphatic endothelial cells (LECs) express Tie2 in both embryonic and adult settings, indicating that Ang signaling occurs in lymphatic vessels. Therefore, we examined whether Ang-1 acts on in vivo lymphatic angiogenesis and in vitro growth of LECs. A chimeric form of Ang-1, cartilage oligomeric matrix protein (COMP)-Ang-1, promotes in vivo lymphatic angiogenesis in mouse cornea. Moreover, we found that COMP-Ang-1 stimulates in vitro colony formation of LECs. These Ang-1-induced in vivo and in vitro effects on LECs were suppressed by soluble Tie2-Fc fusion protein, which acts as an inhibitor by sequestering Ang-1. On the basis of these observations, we propose that Ang signaling regulates lymphatic vessel formation through Tie2. (c) 2005 by The American Society of Hematology.