Qi Jian Hua, Ebrahem Quteba, Moore Nina, Murphy Gillian, Claesson-Welsh Lena, Bond Mark, Baker Andrew, Anand-Apte Bela
Department of Ophthalmic Research, Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA.
Nat Med. 2003 Apr;9(4):407-15. doi: 10.1038/nm846. Epub 2003 Mar 24.
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.
金属蛋白酶组织抑制剂-3（TIMP3）是一类蛋白质家族的四个成员之一，该家族最初是根据其抑制基质金属蛋白酶（MMP）的能力进行分类的。TIMP3编码一种有效的血管生成抑制剂，在索斯比眼底营养不良中发生突变，这是一种伴有黄斑下脉络膜新生血管形成的黄斑变性疾病。在本研究中，我们证明了TIMP3抑制血管内皮生长因子（VEGF）介导的血管生成的能力，并确定了其发生的潜在机制：TIMP3阻断VEGF与VEGF受体-2的结合，并抑制下游信号传导和血管生成。这种特性似乎与其MMP抑制活性无关，表明该分子具有新的功能。
