Repulsive axon guidance molecule Slit3 is a novel angiogenic factor
Repulsive axon guidance molecule Slit3 is a novel angiogenic factor
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DOI：
10.1182/blood-2008-12-193326
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发表时间：
2009-11-05
期刊：
影响因子：
20.3
通讯作者：
Wang, Lianchun
中科院分区：
文献类型：
--
作者：
Zhang, Bing;Dietrich, Ursula M.;Wang, Lianchun
裂缝是大的，分泌排斥轴突引导分子。最近的遗传学研究表明，Slit 3是神经发育所必需的，但非神经元相关的发育过程，如膈肌和肾脏的发生。在这里，我们报告说，Slit 3有效地促进血管生成，这是胚胎发育过程中适当器官形成所必需的过程。我们观察到Slit 3在血管系统中由内皮细胞和血管平滑肌细胞表达和分泌，并且Slit同源受体Robo 1和Robo 4在内皮细胞中普遍表达，这表明Slit 3可能以旁分泌和自分泌方式调节内皮细胞。细胞功能研究表明，Slit 3通过与Robo 4相互作用刺激内皮细胞增殖，促进内皮细胞运动和趋化性，并加速体外内皮细胞血管网络形成，其比活性与血管内皮生长因子相当。此外，Slit 3刺激离体新血管发芽和体内新血管生长。与这些观察结果一致，Slit 3敲除小鼠在胚胎发生期间显示出破坏的血管生成。总之，我们的研究表明，排斥性轴突导向分子Slit 3是一种新的和有效的血管生成因子，并在胚胎发育过程中协调器官发生中促进血管生成。（血。2009; 114：4300-4309）
Slits are large, secreted repulsive axon guidance molecules. Recent genetic studies revealed that the Slit3 is dispensable for neural development but required for non-neuron-related developmental processes, such as the genesis of the diaphragm and kidney. Here we report that Slit3 potently promotes angiogenesis, a process essential for proper organogenesis during embryonic development. We observed that Slit3 is expressed and secreted by both endothelial cells and vascular smooth muscle cells in vasculature and that the Slit cognate receptors Robo1 and Robo4 are universally expressed by endothelial cells, suggesting that Slit3 may act in paracrine and autocrine manners to regulate endothelial cells. Cellular function studies revealed that Slit3 stimulates endothelial-cell proliferation, promotes endothelial-cell motility and chemotaxis via interaction with Robo4, and accelerates endothelial-cell vascular network formation in vitro with a specific activity comparable with vascular endothelial growth factor. Furthermore, Slit3 stimulates neovessel sprouting ex vivo and new blood vessel growth in vivo. Consistent with these observations, the Slit3 knockout mice display disrupted angiogenesis during embryogenesis. Taken together, our studies reveal that the repulsive axon guidance molecule Slit3 is a novel and potent angiogenic factor and functions to promote angiogenesis in coordinating organogenesis during embryonic development. (Blood. 2009; 114:4300-4309)