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MMP14 Cleavage of VEGFR1 in the Cornea Leads to a VEGF-Trap Antiangiogenic Effect.
Han, Kyu-Yeon; Dugas-Ford, Jennifer; Lee, Hyun; Chang, Jin-Hong; Azar, Dimitri T.
Afiliación
  • Han KY; Department of Ophthalmology and Visual Sciences Illinois Eye and Ear Infirmary, University of Illinois at Chicago, Chicago, Illinois, United States.
  • Dugas-Ford J; Department of Ophthalmology and Visual Sciences Illinois Eye and Ear Infirmary, University of Illinois at Chicago, Chicago, Illinois, United States.
  • Lee H; Center for Pharmaceutical Biotechnology and Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, Illinois, United States.
  • Chang JH; Department of Ophthalmology and Visual Sciences Illinois Eye and Ear Infirmary, University of Illinois at Chicago, Chicago, Illinois, United States.
  • Azar DT; Department of Ophthalmology and Visual Sciences Illinois Eye and Ear Infirmary, University of Illinois at Chicago, Chicago, Illinois, United States.
Invest Ophthalmol Vis Sci ; 56(9): 5450-6, 2015 Aug.
Article en En | MEDLINE | ID: mdl-26284550
PURPOSE: To determine the possible antiangiogenic effect of metalloproteinase (MMP) 14 cleavage of vascular endothelial growth factor receptor 1 (VEGFR1) in the cornea. METHODS: Recombinant mouse (rm) VEGFR1 was incubated with various concentrations of recombinant MMP14 to examine proteolysis in vitro. The reaction mixture was analyzed by SDS-PAGE and stained with Coomassie blue. The fragments resulting from rmVEGFR1 cleavage by MMP14 were subjected to Edman degradation, and the amino acid sequences were aligned with rmVEGFR1 sequences. Surface plasmon resonance was used to determine the equilibrium dissociation constant (KD) between MMP14 and rmVEGFR1. The KD value of rmVEGFR1 and the 59.8-kDa cleavage product binding to VEGF-A165 was also determined. Cell proliferation assays were performed in the presence of VEGF-A165 plus the 59.8-kDa VEGFR1 fragment or VEGF-A165 alone. RESULTS: Matrix metalloproteinase 14 binds and cleaves rmVEGFR1 to produce 59.8-kDa (N-terminal fragment, Ig domains 1-5), 35-kDa (C-terminal fragment containing IgG and His-tag), and 21-kDa (Ig domains 6-7) fragments. The 59.8-kDa fragment showed binding to VEGF-A165 and inhibited VEGF-induced endothelial cell mitogenesis. CONCLUSIONS: Our findings suggest that VEGFR1 cleavage by MMP14 in the cornea leads to a VEGF-trap effect, reducing the proangiogenic effect of VEGF-A165, thereby reducing corneal angiogenesis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neovascularización de la Córnea / Córnea / Receptor 1 de Factores de Crecimiento Endotelial Vascular / Factor A de Crecimiento Endotelial Vascular / Metaloproteinasa 14 de la Matriz Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Invest Ophthalmol Vis Sci Año: 2015 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neovascularización de la Córnea / Córnea / Receptor 1 de Factores de Crecimiento Endotelial Vascular / Factor A de Crecimiento Endotelial Vascular / Metaloproteinasa 14 de la Matriz Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Invest Ophthalmol Vis Sci Año: 2015 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos