A novel function for tissue inhibitor of metalloproteinases-3 (TIMP3): inhibition of angiogenesis by blockage of VEGF binding to VEGF receptor-2
A novel function for tissue inhibitor of metalloproteinases-3 (TIMP3): inhibition of angiogenesis by blockage of VEGF binding to VEGF receptor-2
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DOI：
10.1038/nm846
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发表时间：
2003-04-01
期刊：
影响因子：
82.9
通讯作者：
Anand-Apte, B
中科院分区：
文献类型：
--
作者：
Qi, JH;Ebrahem, Q;Anand-Apte, B
金属蛋白酶组织抑制剂3（TIMP 3）是最初根据其抑制基质金属蛋白酶（MMP）的能力分类的蛋白质家族的四个成员之一。编码有效的血管生成抑制剂的TIMP3在Sorsby眼底营养不良中突变，Sorsby眼底营养不良是一种伴有黄斑下脉络膜新生血管形成的黄斑变性疾病。在这项研究中，我们证明了TIMP3抑制血管内皮因子（VEGF）介导的血管生成的能力，并确定了发生这种情况的潜在机制：TIMP3阻断VEGF与VEGF受体2的结合，抑制下游信号传导和血管生成。这种性质似乎是独立的MMP抑制活性，表明这种分子的新功能。
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.