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The Suppressive effect of Largazole, an Inhibitor of Histone Deacetylases, on Inflammatory Corneal Neovascularization |
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The Suppressive effect of Largazole, an Inhibitor of Histone Deacetylases, on Inflammatory Corneal Neovascularization |
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作者:周红颜 文章来源:中山大学中山眼科中心 点击数:411 更新时间:2012/9/13
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Objective Histone deacetylases (HDACs) constitute a family of enzymes that regulate gene transcription by modifying the acetylation level of histone and nonhistone proteins. In this study, we determined the effect of largazole, an inhibitor of HDACs, on inflammatory corneal angiogenesis. Methods and Results In a mouse model of alkali-induced corneal neovascularization (CNV), we found that topical application of largazole to the injured corneas attenuated CNV. Further studies revealed that the treatment of largazole in vivo down-regulated the expression of the pro-angiogenic factors VEGF, FGF, TGF-b and up-regulated the expression of the anti-angiogenic factors Thrombospondin-1, Thrombospondin-2 and ADAMTS-1. Furthermore, largazole inhibited the cell proliferation, migration and pro-angiogenic factor expression of human umbilical vein endothelial cells (HUVECs) in vitro. Conclusions These findings suggest that largazole has therapeutic potential for angiogenesis-related diseases. |
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