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.

    選擇恒遠生物，您將得到高質量的產品、實惠的價格、的服務、快捷的到貨、穩定的貨源、；
 ！我們會定期推出市場活動，及時給您提供足夠的市場*和產品資料！我們提供一切售前支持和售后服務！我們的http://www.26604.cn 可以查到大部分產品詳細信息、價格（具體產品說明書可以找我們索?。貙⒊蔀槟湍蛻舻挠辛ぞ?！