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Neutralization of Bombina variegata peptide 8 suppresses retinal neovascularization in two different murine models: The oxygen-induced retinopathy model and the rhodopsin promoter/VEGF transgenic mouse model
Experimental Eye Research ( IF 3.4 ) Pub Date : 2020-03-05 , DOI: 10.1016/j.exer.2020.107993
Yiyun Yao , Yixuan Yao , Anna M. Demetriades , Ailing Sui , Ting Su , Yanji Zhu , Xi Shen , Bing Xie

Bombina variegata 8 (Bv8), also known as prokineticin-2 (PK-2), is a potent pro-angiogenic factor. However, its role in retinal neovascularization (RNV) remains unknown. In this study, we explored the role of Bv8 in the pathogenesis of RNV. We found that the expression of Bv8 was significantly increased in two different models of retinal nevoacularization: the oxygen-induced retinopathy (OIR) mouse model and the rhodopsin promoter (rho)/VEGF transgenic mouse model. Neutralization of Bv8 by intravitreal injections of its antibody, not only inhibited retinal and subretinal neovascularization but also decreased the mRNA and protein levels of several pro-angiogenic factors. Our in vitro assay showed that recombinant human Bv8 (RhBv8) protein promoted human retinal microvascular endothelial cells (HRECs) tube-formation, cell proliferation and vascular endothelial growth factor receptor 1 (VEGFR1) and receptor 2 (VEGFR2) expression. Our findings suggest that Bv8 could be used as a novel target for the treatment of RNV-related ocular diseases.



中文翻译:

在两个不同的鼠模型中,变种Bombina variegata肽8抑制视网膜新生血管形成:氧致视网膜病模型和视紫红质启动子/ VEGF转基因小鼠模型

Bombina variegata 8(Bv8),也称为prokineticin-2(PK-2),是有效的促血管生成因子。然而,其在视网膜新血管形成(RNV)中的作用仍然未知。在这项研究中,我们探讨了Bv8在RNV发病机理中的作用。我们发现Bv8的表达在视网膜神经眼化的两种不同模型中显着增加:氧诱导性视网膜病(OIR)小鼠模型和视紫红质启动子(rho)/ VEGF转基因小鼠模型。通过玻璃体内注射Bv8来中和Bv8,不仅抑制了视网膜和视网膜下的新生血管形成,而且还降低了一些促血管生成因子的mRNA和蛋白水平。我们的体外分析表明,重组人Bv8(RhBv8)蛋白可促进人视网膜微血管内皮细胞(HREC)的管形成,细胞增殖和血管内皮生长因子受体1(VEGFR1)和受体2(VEGFR2)的表达。我们的研究结果表明Bv8可用作治疗RNV相关眼病的新型靶标。

更新日期:2020-03-05
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