A novel function for tissue inhibitor of metalloproteinases-3 (TIMP3): inhibition of angiogenesis by blockage of VEGF binding to VEGF receptor-2
Abstract
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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TIMP3 is a tissue inhibitor of MMPs that inhibits angiogenesis and tumor cell infiltration and also induces apoptosis.
“TIMP3 is a tissue inhibitor of MMPs that inhibits angiogenesis and tumor cell infiltration and also induces apoptosis (2, 48).”
From MicroRNA 21 Promotes Glioma Invasion by Targeting Matrix Metalloproteinase Regulators (2008) · cites this paper as [48]
Cites
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The Retinal Pigment Epithelium in Visual Function
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Novel functions of TIMPs in cell signaling
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Loss of TIMP3 underlies diabetic nephropathy via FoxO1/STAT1 interplay
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Genetics of age-related macular degeneration: current concepts, future directions
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Sorsby fundus dystrophy—A review of pathology and disease mechanisms
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Self-citation
- Authors
- Qi, J. H., Ebrahem, Q., Moore, N., Murphy, G., Claesson-Welsh, L., Bond, M., Baker, A., & Anand-Apte, B.
- Affiliations
- Cleveland Clinic (US)
- University of Cambridge (GB)
- Bristol Royal Infirmary (GB)
- University of Glasgow (GB)
- Venue
- Nature Medicine
- Published
- 2003-03-24
- Volume
- 9
- Issue
- 4
- Pages
- 407-415
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2166859762
- Cited by
- 658
- References
- 2
- Citations by year
- 2026: 14 · 2025: 10 · 2024: 19 · 2023: 13 · 2022: 33 · 2021: 24 · 2020: 29 · 2019: 31 · 2018: 21 · 2017: 34 · 2016: 33 · 2015: 33 · 2014: 24 · 2013: 35 · 2012: 36
- FWCI
- 14.28
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Eye Institute (R29EY012109, 1 R29 EY12109-01, R01EY016490)
- National Cancer Institute (R01CA106415)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Keywords
- TIMP-3, angiogenesis inhibition, vascular endothelial growth factor, VEGF receptor 2, VEGF binding, Sorsby fundus dystrophy, choroidal neovascularization, macular degeneration, matrix metalloproteinase inhibition, downstream signaling
- MeSH terms
- Cell Division, Cell Line, Endothelium, Humans, Lymphokines, Neovascularization, Pathologic, Phosphorylation, Recombinant Proteins, Endothelial Growth Factors, Tissue Inhibitor of Metalloproteinases, Tissue Inhibitor of Metalloproteinase-3, Intercellular Signaling Peptides and Proteins, Neuropilins, Receptors, Vascular Endothelial Growth Factor, Vascular Endothelial Growth Factors, Vascular Endothelial Growth Factor A
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