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K. Ohno-Matsui, I. Morita, T. Yoshida, T. Uetama, M. Mochizuki; Vascular Endothelial Growth Factor Up-Regulates Pigment Epithelium-Derived Factor Expression via VEGFR-1 in Human Retinal Pigment Epithelial Cells . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1705.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:We previously reported that differentiated retinal pigment epithelial (RPE) cells express high levels of both vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF), and a critical balance between VEGF and PEDF is important to prevent the development of choroidal neovascularization. In the present study, we investigated whether VEGF regulates PEDF expression in differentiated human RPE cells. Methods:Human RPE cells were grown in culture on laminin-coated flasks to produce differentiated features. To demonstrate that the expression of PEDF was mediated by VEGF and its receptors, anti-VEGF monoclonal, anti-VEGFR-1 polyclonal, and anti-VEGFR-2 polyclonal antibodies, and human placenta growth factor (PlGF) were added to the maximally differentiated cells. PEDF expression was examined using RT-PCR and Western blotting methods. Results:Expression of PEDF mRNA and PEDF protein was dramatically down-regulated by neutralizing antibody against VEGF. Differentiated RPE cells expressed both VEGFR-1 and VEGFR-2 mRNA. Neutralization of VEGFR-1 significantly decreased the expression of PEDF mRNA and protein whereas the anti-VEGFR-2 antibody had no effect. Moreover, the addition of PlGF restored the expression of PEDF in the presence of anti-VEGF antibody. Conclusions:These results demonstrate that VEGF secreted by RPE cells up-regulates the expression of PEDF via VEGFR-1 in an autocrine manner. This finding indicates that conventional anti-angiogenic therapy that blocks only VEGF might cause subsequent down-regulation of PEDF expression and, therefore, have an insufficient treatment effect.
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