有缺陷的血管生成是很多疾病的一个共同特点，其中包括与年龄相关的黄斑部退化、动脉粥样硬化、风湿性关节炎和癌症。在这项研究中，John Greenwood及其同事识别出具有以前不知道的功能的一种新颖的血管生成性糖蛋白，即“leucine-rich-alpha-2-glycoprotein 1” (LRG1)， 它通过改变 TGF-β 信号作用来施加其影响。LRG1（在来自“增生型糖尿病性视网膜病变”患者的玻璃体样本中含量增加）通过结合到受体“endoglin”上激发一个血管生成开关，促进“促血管生成”TGF-β信号作用。由抗体介导的LRG1抑制在一个小鼠视网膜受伤模型中减少致病性新血管生成，这说明LRG1对于在眼病中控制病理性血管生成来说是一个可能的治疗目标。（生物谷Bioon.com）
生物谷推荐英文摘要：
Nature doi: 10.1038/nature12345
LRG1 promotes angiogenesis by modulating endothelial TGF-β signalling
Xiaomeng Wang, Sabu Abraham, Jenny A. G. McKenzie, Natasha Jeffs, Matthew Swire, Vineeta B. Tripathi, Ulrich F. O. Luhmann, Clemens A. K. Lange, Zhenhua Zhai, Helen M. Arthur, James W. B. Bainbridge, Stephen E. Moss & John Greenwood
Aberrant neovascularization contributes to diseases such as cancer, blindness and atherosclerosis, and is the consequence of inappropriate angiogenic signalling. Although many regulators of pathogenic angiogenesis have been identified, our understanding of this process is incomplete. Here we explore the transcriptome of retinal microvessels isolated from mouse models of retinal disease that exhibit vascular pathology, and uncover an upregulated gene, leucine-rich alpha-2-glycoprotein 1 (Lrg1), of previously unknown function. We show that in the presence of transforming growth factor-β1 (TGF-β1), LRG1 is mitogenic to endothelial cells and promotes angiogenesis. Mice lacking Lrg1 develop a mild retinal vascular phenotype but exhibit a significant reduction in pathological ocular angiogenesis. LRG1 binds directly to the TGF-β accessory receptor endoglin, which, in the presence of TGF-β1, results in promotion of the pro-angiogenic Smad1/5/8 signalling pathway. LRG1 antibody blockade inhibits this switch and attenuates angiogenesis. These studies reveal a new regulator of angiogenesis that mediates its effect by modulating TGF-β signalling.
