Netrins promote developmental and therapeutic angiogenesis
Netrins promote developmental and therapeutic angiogenesis
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DOI：
10.1126/science.1124704
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发表时间：
2006-08-04
期刊：
影响因子：
56.9
通讯作者：
Li, Dean Y.
中科院分区：
文献类型：
--
作者：
Wilson, Brent D.;Ii, Masaaki;Li, Dean Y.
轴突引导和血管模式有几个共同的引导线索，包括netrin家族中的蛋白质。我们证明，netrin刺激增殖，迁移和管形成的人内皮细胞在体外，这种刺激是独立的已知netrin受体。抑制netrin1a信使RNA在斑马鱼抑制血管发芽，这意味着在脊椎动物发育过程中netrins的proangiogenic rote。我们还表明，netrins在体内缺血模型中加速新血管形成，并在糖尿病小鼠模型中逆转神经病变和血管病变。我们认为netrins具有吸引人的血管和神经引导功能，具有独特的治疗潜力。
Axonal guidance and vascular patterning share several guidance cues, including proteins in the netrin family. We demonstrate that netrins stimulate proliferation, migration, and tube formation of human endothelial cells in vitro and that this stimulation is independent of known netrin receptors. Suppression of netrin1a messenger RNA in zebrafish inhibits vascular sprouting, implying a proangiogenic rote for netrins during vertebrate development. We also show that netrins accelerate neovascularization in an in vivo model of ischemia and that they reverse neuropathy and vasculopathy in a diabetic murine model. We propose that the attractive vascular and neural guidance functions of netrins offer a unique therapeutic potential.