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The Inhibitory Effects of Gold Nanoparticles on VEGF-A-Induced Cell Migration in Choroid-Retina Endothelial Cells

机译:金纳米颗粒对脉络膜-视网膜内皮细胞中VEGF-A诱导的细胞迁移的抑制作用。

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摘要

Background: Vascular endothelial growth factor (VEGF) is upregulated by hypoxia and is a crucial stimulator for choroidal neovascularization (CNV) in age-related macular degeneration and pathologic myopia, as well as retinal neovascularization in proliferative diabetic retinopathy. Retinal and choroidal endothelial cells play key roles in the development of retinal and CNV, and subsequent fibrosis. At present, the effects of gold nanoparticles (AuNPs) on the VEGF-induced choroid-retina endothelial (RF/6A) cells are still unknown. In our study, we investigated the effects of AuNPs on RF/6A cell viabilities and cell adhesion to fibronectin, a major ECM protein of fibrovascular membrane. Furthermore, the inhibitory effects of AuNPs on RF/6A cell migration induced by VEGF and its signaling were studied. Methods: The cell viability assay was used to determine the viability of cells treated with AuNPs. The migration of RF/6A cells was assessed by the Transwell migration assay. The cell adhesion to fibronectin was examined by an adhesion assay. The VEGF-induced signaling pathways were determined by western blotting. Results: The 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) viability assay revealed no cytotoxicity of AuNPs on RF/6A cells. AuNPs inhibited VEGF-induced RF/6A cell migration in a concentration-dependent manner but showed no significant effects on RF/6A cell adhesion to fibronectin. Inhibitory effects of AuNPs on VEGF-induced Akt/eNOS were found. Conclusions: These results suggest that AuNPs are an effective inhibitor of VEGF-induced RF/6A cell migration through the Akt/eNOS pathways, but they have no effects on their cell viabilities and cell adhesion to fibronectin.
机译:背景:缺氧可上调血管内皮生长因子(VEGF),是年龄相关性黄斑变性和病理性近视眼中脉络膜新生血管(CNV)以及增生性糖尿病性视网膜病中视网膜新生血管形成的关键刺激物。视网膜和脉络膜内皮细胞在视网膜和CNV的发展以及随后的纤维化中起关键作用。目前,尚不清楚金纳米颗粒(AuNPs)对VEGF诱导的脉络膜-视网膜内皮细胞(RF / 6A)的影响。在我们的研究中,我们研究了AuNPs对RF / 6A细胞活力和细胞对纤连蛋白(一种纤维血管膜的主要ECM蛋白)的粘附作用。此外,研究了AuNPs对VEGF诱导的RF / 6A细胞迁移的抑制作用及其信号传导。方法:使用细胞活力测定法确定经AuNPs处理的细胞的活力。通过Transwell迁移分析评估RF / 6A细胞的迁移。通过粘附测定法检查细胞对纤连蛋白的粘附。 VEGF诱导的信号传导途径通过蛋白质印迹法确定。结果:3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴化物(MTT)活力测定显示AuNPs对RF / 6A细胞无细胞毒性。 AuNP以浓度依赖的方式抑制VEGF诱导的RF / 6A细胞迁移,但对RF / 6A细胞对纤连蛋白的粘附没有显着影响。发现了AuNP对VEGF诱导的Akt / eNOS的抑制作用。结论:这些结果表明,AuNPs是通过Akt / eNOS途径有效抑制VEGF诱导的RF / 6A细胞迁移,但对它们的细胞活力和细胞对纤连蛋白的粘附没有影响。

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