Wilson Brent D, Ii Masaaki, Park Kye Won, Suli Arminda, Sorensen Lise K, Larrieu-Lahargue Fréderic, Urness Lisa D, Suh Wonhee, Asai Jun, Kock Gerhardus A H, Thorne Tina, Silver Marcy, Thomas Kirk R, Chien Chi-Bin, Losordo Douglas W, Li Dean Y
Program in Human Molecular Biology and Genetics, University of Utah, Salt Lake City, UT 84112, USA.
Science. 2006 Aug 4;313(5787):640-4. doi: 10.1126/science.1124704. Epub 2006 Jun 29.
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 role 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.
轴突导向和血管模式形成共享多种导向线索，包括网蛋白家族中的蛋白质。我们证明，网蛋白在体外可刺激人内皮细胞的增殖、迁移和管形成，且这种刺激独立于已知的网蛋白受体。斑马鱼中网蛋白1a信使核糖核酸的抑制会抑制血管芽生，这意味着在脊椎动物发育过程中网蛋白具有促血管生成作用。我们还表明，在缺血的体内模型中网蛋白可加速新血管形成，并且在糖尿病小鼠模型中它们可逆转神经病变和血管病变。我们提出，网蛋白具有吸引力的血管和神经导向功能具有独特的治疗潜力。
