期刊
NATURE MEDICINE
卷 9, 期 4, 页码 407-415出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nm846
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资金
- NCI NIH HHS [R01 CA106415] Funding Source: Medline
- NEI NIH HHS [R29 EY012109, 1 R29 EY12109-01, R01 EY016490] Funding Source: Medline
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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