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Inyoung Chung, Hyemin Seong, Sang Soo Kang, Jong Moon Park, Seong Wook Seo; Resveratrol suppresses the VEGF expression by inhibition of the CXCR4 Expression in ARPE-19 cells. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4621.
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© ARVO (1962-2015); The Authors (2016-present)
Angiogenesis is one of the typical reasons that lead to loss of vision in the eye. Therefore, the inhibition of angiogenesis is an important therapeutic mechanism in eye research. Res (3,5,4 '-trihydroxy-trans-stilbene) is a kind of polyphenol, which mainly found in grape skins and red wine. This natural object activates the NAD-dependent deacetylase sirtuin-1 (Sirt-1). The main target of Sirt-1 is NF-KB, that is known as which interaction with C-X-C chemokine receptor type 4 (CXCR4). CXCR4, stromal cell-derived factor-1 (SDF-1) -specific receptor, is main factor of angiogenesis. The present study aims to reveal the effects of Res on suppression of the CXCR4 mediated vascular endothelial growth factor (VEGF) expression in retinal pigment epithelial(RPE) cells.
Res was Pre-treated for 2 hours in ARPE-19 Cell lines. After that, Cobalt(II) chloride(CoCl2) was treated with Res for 6 hours as a inducer of chemical hypoxia. Then, protein and mRNA were extracted. NF-kB, SDF-1 and CXCR4 protein expressions were measured by western blotting analysis. Sirt-1, SDF-1, VEGF mRNA expressions were measured by RT-PCR, ELASA to observe the effects of Res.
CoCl2 using chemical hypoxia induced the increasing of the phosphorylation of NF-kB and protein expression of SDF-1, CXCR4. In Res co-treating, activation of Sirt-1 was increased. Phosphorylation of NF-KB and protein expression of SDF-1, CXCR4 were decreased in dose-, time-dependent manner. Also mRNA expression of VEGF was decreased.
Through this study, we demonstrated that Res inhibits VEGF expression in the RPE cell. When Sirt1 activated by Res, it suppresses NF-kB to down-regulate NF-kB pathway. Then expression of CXCR4 is reduced that inhibits transcription of VEGF, CXCR4 downstream angiogenic factor. Furthermore we clarified that CXCR4 is downstream factor of NF-kB pathway.
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