Down-regulation of Vascular Endothelial Growth Factor and Up-regulation of Pigment Epithelium-derived Factor A POSSIBLE MECHANISM FOR THE ANTI-ANGIOGENIC ACTIVITY OF PLASMINOGEN KRINGLE 5

Published on Mar 15, 2002in Journal of Biological Chemistry4.238
· DOI :10.1074/JBC.M108004200
G Gao5
Estimated H-index: 5
(MUSC: Medical University of South Carolina),
Yan Li4
Estimated H-index: 4
(MUSC: Medical University of South Carolina)
+ 4 AuthorsJian Xing Ma73
Estimated H-index: 73
(MUSC: Medical University of South Carolina)
Abstract 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 hypoxia-inducible factor-1α, 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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