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K. Kim, Y. S. Yu, J. Kim, K.-H. Park, J. Kim, K.-W. Kim; Sterol Regulatory Element-Binding Proteins (SREBP)-Mediated VEGF Expression by LDL & VLDL in Retinal Pigment Epithelial Cells. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2195.
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© ARVO (1962-2015); The Authors (2016-present)
To determine the sterol regulatory element-binding proteins (SREBPs)-mediated vascular endothelial growth factor (VEGF) expression in retinal pigment epithelial (RPE) cells under hyper-cholesterolemic condition
In RPE of Apo-E2 transgenic mice, Sudan black B staining and immunohistochemistry for VEGF was done. In human retinal pigment epithelial cell line (ARPE-19) treated with human low density lipoproteins (LDL) or very low density lipoproteins (VLDL) respectively, expression of LDLR, VLDLR, SREBPs, and VEGF was measured via western blot analysis. SREBP binding to the VEGF promoter was analyzed by electrophoretic mobility shift assays.
In RPE of Apo-E2 transgenic mice, Sudan black B staining was markedly defined and VEGF expression was increased compared to control. In ARPE19 with LDL or VLDL treatment, VEGF and SREBPs expression increased. Interestingly, VLDLR expression decreased, while LDLR did not change.
Our data supposed lipid up-taken via VLDLR may activate SREBPs, transcription factors of lipid synthesis, and increase the expression of VEGF. Therefore, we suggest that activation of SREBP-1 resulting from lipid uptake plays an important role in angiogenesis of the RPE layer.
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