Inhibition of Basic Fibroblast Growth Factor Induced Rat Corneal Angiogenesis by a Urokinase Plasminogen Activator Receptor Antagonist.
- Author:
Ja Young LEE
1
;
Sung Kun CHUNG
;
David G HWANG
Author Information
1. Department of Ophthalmology, Catholic University, Medical College, Seoul, Korea.
- Publication Type:Original Article
- Keywords:
Angiogenesis;
Corneal pocket assay;
Urokinase plasminogen activator receptor antagonist
- MeSH:
Animals;
Corneal Neovascularization*;
Fibroblast Growth Factor 2*;
Fibroblasts;
Hydrogel;
Immunoglobulin G;
Plasminogen Activators*;
Plasminogen*;
Rats*;
Urokinase-Type Plasminogen Activator*
- From:Journal of the Korean Ophthalmological Society
1997;38(4):553-558
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
During angiogenesis, binding of urokinase plasminogen activator(uPA) and its receptor(uPAR) has been implicated as an important component of the angiogenesis pathway. We have produced a high-affinity competitive antagonist for the uPA receptor consisting of a fusion protein linking the endothelial growth factor(EGF)-like domain of uPA(residues 1-48) to the Fc domain of IgG. To determine whether this recombinant murine uPA1-48-IgG fusion protein could interfere with angiogenesis, we studied the effect of this compound on rat corneal angiogenesisinduced by basic fibroblast growth factor(bFGF). A hydrogel disk containing 250ng of bFGF and 4.2ug of uPA1-48-IgG fusiong protein in seven eyes, 250ug of bFGF and 4.2ug of phosphate-buffered saline(PBS) in another sseven eyes were implanted intrastromally 1.5mm from the superior limbus. At five days post-implantation of bFGF disk, the eyes treated with uPA1-48IgG fusion protein had reduced angiogenesis (mean score=3.1) compared with the PBS-treated controls(mean score=6.1)(P<0.05, Wilcoxon rank sum test). In a rat corneal pocket assay, murine uPA1-48-IgG fusion protein appears to inhibit bFGF-induced angiogenesis. Compounds that block uPAR binding of uPA may have therapeutic potential as anti-angiogenic agents.
