High Concentrations of Uric Acid Inhibit Endothelial Cell Migration via miR-663 Which Regulates Phosphatase and Tensin Homolog by Targeting Transforming Growth Factor-β1
High Concentrations of Uric Acid Inhibit Endothelial Cell Migration via miR-663 Which Regulates Phosphatase and Tensin Homolog by Targeting Transforming Growth Factor-β1
复制标题
高浓度尿酸通过 miR-663 抑制内皮细胞迁移，miR-663 通过靶向转化生长因子-β1 调节磷酸酶和张力蛋白同系物。
DOI：
10.1111/micc.12200
复制
发表时间：
2015-05-01
期刊：
影响因子：
2.4
通讯作者：
Wu, Di
中科院分区：
文献类型：
--
作者：
Hong, Quan;Yu, Shandong;Wu, Di
microRNAs是否参与内皮功能障碍HUA仍不清楚。先前的一项研究表明，在HUA条件下，miR-663是内皮细胞microRNA表达差异最显著的。一些研究表明，miR-663靶基因和TGF-1通过抑制10号染色体上缺失的PTEN来促进内皮细胞迁移。因此，我们假设HUA通过miR-663抑制内皮细胞迁移，miR-663通过靶向TGF-1调节PTEN。方法采用spcr分析检测miR-663的表达水平。荧光素酶测定验证miR-663是否直接靶向TGF-1。Western blot检测TGF-1和PTEN的表达水平。将miR-663抑制剂和TGF-1和PTEN特异性sirna分别转染到EA.hy926细胞中，分别抑制miR-663、TGF-1和PTEN的表达。采用伤口愈合实验测定EA.hy926细胞的迁移能力。结果smir -663在hua刺激的内皮细胞和高尿酸血症患者及动物血清中表达水平较高。TGF-1被miR-663直接靶向。内皮细胞miR-663在HUA条件下上调，HUA通过靶向TGF-1的miR-663抑制内皮细胞迁移。因此，TGF-1以pten依赖的方式调节细胞迁移。结论hua通过miR-663抑制内皮细胞迁移，miR-663通过靶向TGF-1调控PTEN。
BackgroundWhether microRNAs participate in endothelial dysfunction HUA remains unknown. A previous study indicated that miR-663 was the most significantly differentially expressed endothelial microRNA under HUA conditions. Some studies have demonstrated that the miR-663 target gene and TGF-1, promoted endothelial cell migration by inhibiting PTEN deleted on chromosome 10. Therefore, we hypothesized that HUA inhibits endothelial migration via miR-663, which regulates PTEN by targeting TGF-1.MethodsPCR analysis was performed to determine miR-663 expression levels. A luciferase assay was performed to validate whether miR-663 targets TGF-1 directly. Western blot analysis was performed to determine TGF-1 and PTEN expression levels. An miR-663 inhibitor and TGF-1- and PTEN-specific siRNAs were transfected into EA.hy926 cells to inhibit miR-663, TGF-1, and PTEN expression, respectively. A wound healing assay was performed to determine the migratory ability of EA.hy926 cells.ResultsmiR-663 had higher expression levels in HUA-stimulated endothelial cells and in the sera of hyperuricemic patients and animals. TGF-1 was targeted directly by miR-663. Endothelial miR-663 was up-regulated under HUA conditions, and HUA inhibited endothelial cell migration via miR-663, which targeted TGF-1. Thus, TGF-1 regulated cell migration in a PTEN-dependent manner.ConclusionHUA inhibits endothelial cell migration via miR-663, which regulates PTEN by targeting TGF-1.