Resolvin D1 Modulates the Intracellular VEGF-Related miRNAs of Retinal Photoreceptors Challenged With High Glucose
Resolvin D1 Modulates the Intracellular VEGF-Related miRNAs of Retinal Photoreceptors Challenged With High Glucose
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DOI：
10.3389/fphar.2020.00235
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发表时间：
2020-03-06
影响因子：
5.6
通讯作者：
D'Amico, Michele
中科院分区：
文献类型：
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作者：
Maisto, Rosa;Trotta, Maria Consiglia;D'Amico, Michele
用升高的葡萄糖浓度（30 mM）刺激视网膜光感受器96 h，作为糖尿病视网膜病变体外模型，以研究Resolvin D1（50 nM）对新血管形成的作用。在暴露于HG的光感受器中或在由这些细胞释放的外来体中评估VEGF和抗血管生成miR-20 a-3 p、miR-20 a-5 p、miR-106 a-5 p和miR-20 b表达。高糖增加了VEGF水平，同时降低了光感受器和外泌体中抗血管生成miRNA的含量。RvD 1逆转了葡萄糖损伤在光感受器和外泌体促血管生成潜力中的作用，用HUVEC血管生成测定进行了测试。通过激活FPR 2受体，RvD 1调节了抗血管生成miRNA的表达，这降低了VEGF，以及原代视网膜细胞释放的外泌体的促血管生成潜力。HUVEC转染miR-20 a-3 p、miR-20 a-5 p、miR-106 a-5 p和miR-20 b miRNAs，然后暴露于来自光感受器的外来体，证实了VEGF相关的miRNAs机制和RvD 1的抗血管生成作用。
Stimulation of retinal photoreceptors with elevated glucose concentration (30 mM) for 96 h, served as diabetic retinopathy in vitro model to study Resolvin D1 (50 nM) effects on neovascularization. VEGF and anti-angiogenic miR-20a-3p, miR-20a-5p, miR-106a-5p, and miR-20b expression was assessed either in photoreceptors exposed to HG or in exosomes released by those cells. High glucose increased VEGF levels and concurrently decreased anti-angiogenic miRNAs content in photoreceptors and exosomes. RvD1 reverted the effects of glucose damage in photoreceptors and exosomal pro-angiogenic potential, tested with the HUVEC angiogenesis assay. By activating FPR2 receptor, RvD1 modulated both the expression of anti-angiogenic miRNA, which decrease VEGF, and the pro-angiogenic potential of exosomes released by primary retinal cells. HUVEC transfection with miR-20a-3p, miR-20a-5p, miR-106a-5p, and miR-20b antagomirs, followed by exposure to exosomes from photoreceptors, confirmed the VEGF-related miRNAs mechanism and the anti-angiogenic effects of RvD1.