Molecular Mechanisms Mediating Antiangiogenic Action of the Urokinase Receptor-Derived Peptide UPARANT in Human Retinal Endothelial Cells

Abstract

These findings indicate that UPARANT exerts its antiangiogenic effects through the inhibition of the downstream signaling activated by angiogenic factors such as VEGF-A.

The Urokinase Receptor-Derived Peptide UPARANT Recovers Dysfunctional Electroretinogram and Blood–Retinal Barrier Leakage in a Rat Model of Diabetes

“…In this respect, there is evidence that UPARANT acts on human retinal endothelial cells by preventing VEGF-induced membrane permeability. 16 FIGURE 3. UPARANT restores ERG responses.…”

“…Indeed, we have found ameliorated BRB leakage after UPARANT inhibition of the uPA/uPAR system, which is in line with the fact that uPA/uPAR upregulation participates to BRB breakdown in DR. [9][10][11] In addition, UPARANT ameliorates BRB leakage by restoring altered levels of tight junction proteins in mouse models of either oxygen-induced retinopathy or AMD 20,22 and prevents the VEGF-induced permeability in a monolayer of human retinal endothelial cells. 16…”

“…9,10 uPA/uPAR levels increase in retinal endothelial cells in response to both oxidative stress and VEGF increase caused by high glucose, generating a proteolytic cascade that has detrimental effects on cell permeability. 10,11,[16][17][18][19] In addition, upregulated uPA/uPAR would result in the increased expression of extracellular metalloproteinases 9 and intracellular effectors 20 that concur to BRB breakdown.…”

“…UPARANT has been found to reduce VEGF-induced angiogenesis both in vitro and in vivo. 16,21,22 In particular, in mouse models of neovascular ocular pathologies, intravitreal administration of UPARANT prevents the onset of neovascularization and BRB leakage through the inhibition of proangiogenic and inflammatory factors and also prevents electroretinogram (ERG) dysfunction. 20,22 In the present study, we investigated the effect of systemic UPARANT in a therapeutic setting on diabetes-induced early DR using streptozotocin-treated rats (STZ-rats).…”

Anti‐angiogenic effect of quercetin and its 8‐methyl pentamethyl ether derivative in human microvascular endothelial cells

“…Briefly, 24 hours before the experiment, cells (1 × 10 4 ) were shifted to a medium containing 0.25% serum and then were suspended in 200 µL of the same medium containing Q or its derivatives (25 μmol/L) or in 200 µL retinoblastoma CM containing Q or 8MQPM (25 μmol/L). The mixtures were seeded in 96 well plates covered with polymerized growth factor‐reduced Matrigel matrix, incubated for 4 hours (37°C, 5% CO 2 ) and photographed at 100× magnification using an inverted Leica DM IRB microscope equipped with a charge‐coupled device (CCD) camera, as previously described …”