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
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
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DOI：
10.1074/jbc.m108004200
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发表时间：
2002-03-15
影响因子：
4.8
通讯作者：
Ma, JX
中科院分区：
文献类型：
--
作者：
Gao, GQ;Li, Y;Ma, JX
我们之前已经证明，玻璃体内注射纤溶酶原kringle5(K5)，一种有效的血管生成抑制物，可以抑制缺血诱导的大鼠视网膜新生血管。在此，我们报道K5以剂量依赖的方式下调血管细胞和视网膜中的内源性血管生成刺激因子血管内皮生长因子(VEGF)和上调血管生成抑制因子色素上皮衍生因子(PEDF)。K5对视网膜中血管内皮生长因子和PEDF的调节与其抗血管生成作用有关。K5也改变了视网膜中血管内皮生长因子和PEDF的RNA水平。K5抑制低氧诱导因子-1α的p42/p44蛋白活化和核转位，这可能是其下调血管内皮细胞生长因子表达的机制之一。下调内源性血管生成刺激因子和上调内源性血管生成抑制因子，从而恢复血管生成调控的平衡，可能是K5抗血管生成活性的机制之一。
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 downregulates 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-la, 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.