Down-regulation of Vascular Endothelial Growth Factor and Up-regulation of Pigment Epithelium-derived Factor

Gao, Guoquan; Li, Yan; Gee, Stephen H.; Dudley, Andrew C.; Fant, James; Crosson, Craig E.; Ma, Jian-Xing

doi:10.1074/jbc.m108004200

Cited by 120 publications

(87 citation statements)

References 39 publications

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“…This is the first study reporting expression of VDAC1 in HUVEC plasma membranes. A receptor binding assay on endothelial cells using 125 I-K5 was previously reported by another group (40); however, no specific binding of K5 to endothelial cells was detected (40). We obtained similar negative results when we used iodination techniques producing tyrosine modification of K5.…”

Section: Analyses Of Sequence Similarities Between Sk and Humansupporting

confidence: 72%

The Voltage-dependent Anion Channel Is a Receptor for Plasminogen Kringle 5 on Human Endothelial Cells

Gonzalez-Gronow

Kalfa

Johnson

et al. 2003

Journal of Biological Chemistry

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Human plasminogen contains structural domains that are termed kringles. Proteolytic cleavage of plasminogen yields kringles 1-3 or 4 and kringle 5 (K5), which regulate endothelial cell proliferation. The receptor for kringles 1-3 or 4 has been identified as cell surfaceassociated ATP synthase; however, the receptor for K5 is not known. Sequence homology exists between the plasminogen activator streptokinase and the human voltagedependent anion channel (VDAC); however, a functional relationship between these proteins has not been reported. A streptokinase binding site for K5 is located between residues Tyr 252 -Lys 283 , which is homologous to the primary sequence of VDAC residues Tyr 224 -Lys 255 . Antibodies against these sequences react with VDAC and detect this protein on the plasma membrane of human endothelial cells. K5 binds with high affinity (K d of 28 nM) to endothelial cells, and binding is inhibited by these antibodies. Purified VDAC binds to K5 but only when reconstituted into liposomes. K5 also interferes with mechanisms controlling the regulation of intracellular Ca 2؉ via its interaction with VDAC. K5 binding to endothelial cells also induces a decrease in intracellular pH and hyperpolarization of the mitochondrial membrane. These studies suggest that VDAC is a receptor for K5.

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Section: Analyses Of Sequence Similarities Between Sk and Humansupporting

confidence: 72%

The Voltage-dependent Anion Channel Is a Receptor for Plasminogen Kringle 5 on Human Endothelial Cells

Gonzalez-Gronow

Kalfa

Johnson

et al. 2003

Journal of Biological Chemistry

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“…Decreased PEDF levels in the retina have been shown to be implicated in the pathogenesis of diabetic macular edema and proliferative diabetic retinopathy (Gao et al 2002, Zhang et al 2006. Previously, we reported that PEDF is a potent anti-inflammatory factor, inhibiting expression of proinflammatory factors, i.e.…”

Section: Introductionmentioning

confidence: 99%

Pigment epithelium-derived factor mitigates inflammation and oxidative stress in retinal pericytes exposed to oxidized low-density lipoprotein

Zhang¹,

Wang²,

Dashti³

et al. 2008

Journal of Molecular Endocrinology

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Oxidized and/or glycated low-density lipoprotein (LDL) may mediate capillary injury in diabetic retinopathy. The mechanisms may involve pro-inflammatory and pro-oxidant effects on retinal capillary pericytes. In this study, these effects, and the protective effects of pigment epithelium-derived factor (PEDF), were defined in a primary human pericyte model. Human retinal pericytes were exposed to 100 mg/ml native LDL (N-LDL) or heavily oxidized glycated LDL (HOG-LDL) with or without PEDF at 10-160 nM for 24 h. To assess pro-inflammatory effects, monocyte chemoattractant protein-1 (MCP-1) secretion was measured by ELISA, and nuclear factor-kB (NF-kB) activation was detected by immunocytochemistry. Oxidative stress was determined by measuring intracellular reactive oxygen species (ROS), peroxynitrite (ONOO K ) formation, inducible nitric oxide synthase (iNOS) expression, and nitric oxide (NO) production. The results showed that MCP-1 was significantly increased by HOG-LDL, and the effect was attenuated by PEDF in a dose-dependent manner. PEDF also attenuated the HOG-LDL-induced NF-kB activation, suggesting that the inhibitory effect of PEDF on MCP-1 was at least partially through the blockade of NF-kB activation. Further studies demonstrated that HOG-LDL, but not N-LDL, significantly increased ONOO K formation, NO production, and iNOS expression. These changes were also alleviated by PEDF. Moreover, PEDF significantly ameliorated HOG-LDL-induced ROS generation through up-regulation of superoxide dismutase 1 expression. Taken together, these results demonstrate proinflammatory and pro-oxidant effects of HOG-LDL on retinal pericytes, which were effectively ameliorated by PEDF. Suppressing MCP-1 production and thus inhibiting macrophage recruitment may represent a new mechanism for the salutary effect of PEDF in diabetic retinopathy and warrants more studies in future.

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“…Both VEGF and PEDF are active in angiogenesis and motoneuron survival. In the vascular endothelial cell system, VEGF and PEDF have counterbalancing proangiogenic and antiangiogenic activities, respectively (17,(19)(20)(21)(22)(23). In motoneurons, both PEDF and VEGF function in concert as neurotrophic͞neuroprotective agents (24)(25)(26)(27).…”

mentioning

confidence: 99%

Identification of the antivasopermeability effect of pigment epithelium-derived factor and its active site

Liu

Ren

Cooper

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

122

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Vascular permeability plays a key role in a wide array of lifethreatening and sight-threatening diseases. Vascular endothelial growth factor can increase vascular permeability. Using a model system for nonproliferative diabetic retinopathy, we found that pigment epithelium-derived factor (PEDF) effectively abated vascular endothelial growth factor-induced vascular permeability. A 44-amino acid region of PEDF was sufficient to confer the antivasopermeability activity. Additionally, we identified four amino acids (glutamate-101, isoleucine-103, leucine-112, and serine-115) critical for this activity. PEDF, or a derivative, could potentially abate or restore vision loss from diabetic macular edema. Furthermore, PEDF may represent a superior therapeutic approach to sepsis-associated hypotension, nephrotic syndrome, and other sight-threatening and life-threatening diseases resulting from excessive vascular permeability.

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Down-regulation of Vascular Endothelial Growth Factor and Up-regulation of Pigment Epithelium-derived Factor

Cited by 120 publications

References 39 publications

The Voltage-dependent Anion Channel Is a Receptor for Plasminogen Kringle 5 on Human Endothelial Cells

The Voltage-dependent Anion Channel Is a Receptor for Plasminogen Kringle 5 on Human Endothelial Cells

Pigment epithelium-derived factor mitigates inflammation and oxidative stress in retinal pericytes exposed to oxidized low-density lipoprotein

Identification of the antivasopermeability effect of pigment epithelium-derived factor and its active site

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