A novel function for tissue inhibitor of metalloproteinases-3 (TIMP3): inhibition of angiogenesis by blockage of VEGF binding to VEGF receptor-2
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.
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关键词：
Humans Endothelium Cell Line Tissue Inhibitor of Metalloproteinases Tissue Inhibitor of Metalloproteinase-3 Receptors, Vascular Endothelial Growth Factor Intercellular Signaling Peptides and Proteins Vascular Endothelial Growth Factor A Recombinant Proteins Neuropilins
DOI：
10.1038/nm846
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年份：
2003
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