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Título: | TIMP-1 promotes VEGF-induced neovascularization in the retina |
Fecha de publicación: | 2001 |
Editorial: | Murcia : F. Hernández |
ISSN: | 0213-3911 |
Materias relacionadas: | CDU::6 - Ciencias aplicadas::61 - Medicina::617 - Cirugía. Ortopedia. Oftalmología |
Palabras clave: | VEGF Retinal neovascularization |
Resumen: | Proteolysis of vascular basement membranes and surrounding extracellular matrix is a critica1 early step in neovascularization. It requires alteration of the balance between matrix metalloproteinases (MMPs) and proteins that bind to and inactivate MMPs, tissue inhibitors of metalloproteinases (TIMPs). TIMP-1 has been demonstrated to inhibit neovascularization in chick chorioallantoic membranes. However, TIMP-1 has also been shown to either promote or inhibit cell proliferation and migration in different settings. To determine whether genetic alteration of the MMPDIMP-1 ratio would alter retinal neovascularization, we crossed mice that express vascular endothelial growth factor (VEGF) in photoreceptors with TIMP-1-deficient mice or mice that overexpress TIMP-1. Compared to VEGF transgenepositive/ TIMP-1-sufficient mice, VEGF transgenepositive1TIMP- 1-deficient mice showed smaller neovascular lesions. There was also no difference between the two groups of mice in the appearance of the neovascularization by light or electron microscopy. Compound VEGFITIMP-1 transgenic mice had increased expression of both VEGF and TIMP-1 in the retina, and had more neovascularization than mice that had increased expression of VEGF alone. These gainand loss-of-function data suggest that alteration of the TIMP-1MMP ratio modulates retinal neovascularization in a complex manner and not simply by altering the proteolytic activity and thereby invasiveness of endothelial cells. |
Autor/es principal/es: | Yamada, E. Tobe, T. Yamada, H. Okamoto, N. Zack, D.J. Werb, Z. Soloway, P.D. Campochiaro, P.A. |
Forma parte de: | Histology and histopathology |
URI: | http://hdl.handle.net/10201/20634 |
Tipo de documento: | info:eu-repo/semantics/article |
Número páginas / Extensión: | 11 |
Derechos: | info:eu-repo/semantics/openAccess |
Aparece en las colecciones: | Vol.16, nº 1 (2001) |
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TIMP1 promotes VEGFinduced neovascularization in the retina.pdf | 5,76 MB | Adobe PDF | Visualizar/Abrir |
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