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首页> 外文期刊>Journal of Cellular Physiology >Novel mechanism for age-related macular degeneration: an equilibrium shift between the angiogenesis factors VEGF and PEDF.
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Novel mechanism for age-related macular degeneration: an equilibrium shift between the angiogenesis factors VEGF and PEDF.

机译：小说年龄相关性黄斑的机制变性:之间的一个平衡转变血管生成因子VEGF和PEDF。

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We investigated gene expression profiles of vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) in differentiated and non-differentiated retinal pigment epithelial (RPE) cells during oxidative stress. Human RPE cells were grown in culture on laminin-coated flasks to obtain differentiated features. Cells cultured on plastic were used as non-differentiated controls. After confluence, hydrogen peroxide (H2O2) was added for 48 h, then, total RNA was extracted and used for RT-PCR and Northern blot analysis. Medium conditioned by RPE was used for ELISA, Western blotting, and in vitro angiogenesis assay. As a result, differentiated RPE cells expressed significantly higher levels of VEGF protein, as compared to their non-differentiated counterparts. The expression pattern remained consistent even after cellular exposure to H2O2. Conversely, while elevated levels of PEDF transcript and protein were seen in differentiated RPE cells, compared to non-differentiated cells, a marked decrease at both PEDF mRNA and protein levels was seen after treatment with H2O2. Moreover, this decrease in PEDF expression was dosage dependent. In in vitro angiogenesis assay, conditioned medium from differentiated human RPE cells after exposure to H2O2 showed a dramatic increase in tubular formation and migratory activity of microvascular endothelial cells. These data suggest that, in physiological conditions, a critical balance between PEDF and VEGF exists, and PEDF may counteract the angiogenic potential of VEGF. Under oxidative stress, PEDF decreases disrupting this balance. This equilibrium shift may be significant in promoting a pathological condition of RPE cells and contributing to choroidal neovascularization in age-related macular degeneration. Copyright 2001 Wiley-Liss, Inc.
机译：我们调查的基因表达谱血管内皮生长因子(VEGF)和色素epithelium-derived因子(PEDF)分化和non-differentiated视网膜色素上皮(RPE)细胞在氧化压力。laminin-coated烧瓶获得差异化特性。non-differentiated控制。过氧化氢(H2O2)添加了48 h,然后,总RNA提取并用于rt - pcr和北部污点分析。RPE用于ELISA、免疫印迹和体外血管生成试验。显著分化RPE细胞表达更高水平的VEGF蛋白相比non-differentiated同行。表达式模式即使保持一致细胞暴露于过氧化氢。高浓度的PEDF转录和蛋白质被认为在分化RPE细胞,相比non-differentiated细胞明显减少过后PEDF mRNA和蛋白水平治疗与过氧化氢。PEDF表达式是剂量依赖。血管生成试验,条件培养基分化人类接触后RPE细胞过氧化氢管显示一个戏剧性的增加形成和微血管的迁徙活动内皮细胞。生理条件下,一个关键的平衡PEDF与VEGF的存在,PEDF可能抵消VEGF的血管生成潜力。在氧化应激,PEDF减少干扰这种平衡。显著促进病理条件RPE细胞,导致脉络膜的新血管形成在年龄相关性黄斑变性。

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