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Papers In Press, published online ahead of print January 8, 2002
Department of Ophthalmology, Medical University of South Carolina, Charleston, SC 29425
Corresponding Author: majx{at}musc.edu
We have previously shown that intravitreal injection of plasminogen kringle 5 (K5), a potent angiogenic inhibitor, inhibits ischemia-induced retinal neovascularization in a rat model. Here we report that K5 down-regulates an endogenous angiogenic stimulator, vascular endothelial growth factor (VEGF) and up-regulates an angiogenic inhibitor, pigment epithelium-derived factor (PEDF) in a dose-dependent manner in vascular cells and in the retina. The regulation of VEGF and PEDF by K5 in the retina correlates with its anti-angiogenic effect in a rat model of ischemia-induced retinopathy. Retinal RNA levels of VEGF and PEDF are also changed by K5. K5 inhibits the p42/p44 MAP kinase activation and nuclear translocation of HIF-1
J. Biol. Chem, 10.1074/jbc.M108004200
Submitted on August 20, 2001
Revised on November 26, 2001
Accepted on January 8, 2002
Down-regulation of VEGF and up-regulation of PEDF: A possible mechanism for the anti-angiogenic activity of plasminogen Kringle 5
, which may be responsible for the down-regulation of VEGF. Down-regulation of endogenous angiogenic stimulators and up-regulation of endogenous angiogenic inhibitors, thus leading toward restoration of the balance in angiogenic control, may represent a mechanism for the anti-angiogenic activity of K5.
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