A novel function for tissue inhibitor of metalloproteinases-3 (TIMP3): inhibition of angiogenesis by blockage of VEGF binding to VEGF receptor-2

被引：520

作者：

Qi, JH

Ebrahem, Q

Moore, N

Murphy, G

Claesson-Welsh, L

Bond, M

Baker, A

Anand-Apte, B

机构：

[1] Cleveland Clin Fdn, Cole Eye Inst, Dept Ophthalm Res, Cleveland, OH 44195 USA

[2] Univ Cambridge, Inst Med Res, Dept Oncol, Cambridge, England

[3] Uppsala Univ, Dept Genet, Vasc Biol Unit, Rudbeck Lab, Uppsala, Sweden

[4] Uppsala Univ, Dept Pathol, Vasc Biol Unit, Rudbeck Lab, Uppsala, Sweden

[5] Univ Bristol, Bristol Royal Infirm, Bristol Heart Inst, Bristol, Avon, England

[6] Univ Glasgow, Dept Med & Therapeut, Glasgow, Lanark, Scotland

[7] Cleveland Clin Fdn, Lerner Res Inst, Dept Cell Biol, Cleveland, OH 44195 USA

来源：

NATURE MEDICINE | 2003年 / 9卷 / 04期

关键词：

D O I：

10.1038/nm846

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Tissue inhibitor of metalloproteinases-3 (TIMP3) is one of four members of a family of proteins that were originally classified according to their ability to inhibit matrix metalloproteinases (MMP). TIMP3, which encodes a potent angiogenesis inhibitor, is mutated in Sorsby fundus dystrophy, a macular degenerative disease with submacular choroidal neovascularization. In this study we demonstrate the ability of TIMP3 to inhibit vascular endothelial factor (VEGF)-mediated angiogenesis and identify the potential mechanism by which this occurs: TIMP3 blocks the binding of VEGF to VEGF receptor-2 and inhibits downstream signaling and angiogenesis. This property seems to be independent of its MMP-inhibitory activity, indicating a new function for this molecule.

引用

页码：407 / 415

页数：9

共 46 条

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