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Background: Whether 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-β1, 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-β1., Methods: PCR analysis was performed to determine miR-663 expression levels. A luciferase assay was performed to validate whether miR-663 targets TGF-β1 directly. Western blot analysis was performed to determine TGF-β1 and PTEN expression levels. An miR-663 inhibitor and TGF-β1- and PTEN-specific siRNAs were transfected into EA.hy926 cells to inhibit miR-663, TGF-β1, and PTEN expression, respectively. A wound healing assay was performed to determine the migratory ability of EA.hy926 cells., Results: miR-663 had higher expression levels in HUA-stimulated endothelial cells and in the sera of hyperuricemic patients and animals. TGF-β1 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-β1. Thus, TGF-β1 regulated cell migration in a PTEN-dependent manner., Conclusion: HUA inhibits endothelial cell migration via miR-663, which regulates PTEN by targeting TGF-β1., (© 2015 John Wiley & Sons Ltd.)

Background/Aims: Reports have suggested that the traditional Chinese medicine Smilacis Glabrae Rhizoma attenuates hyperuricemia, but its mechanism is unclear. Our previous study demonstrated that uric acid could induce the generation of reactive oxygen species(ROS), which subsequently cause endothelial dysfunction. Therefore, we focused on the oxidative stress process. In this study, we would use LC-MS and bioinformatic analysis to investigate the underlying mechanism. Methods: We utilized LC-MS to reveal the differential protein expression in the kidneys of rats in the hyperuricemia group and the Smilacis Glabrae Rhizoma treatment group and then subjected the differentially expressed proteins to bioinformatic analysis. We also determined the serum ROS level of the two groups. According the above results, we built our hypothesis and performed in vitro experiments to validate this hypothesis. Results: We found that catalase was upregulated in the group treated with Smilacis Glabrae Rhizoma, and the level of reactive oxygen species was higher in the hyperuricemia group. Thus, we speculated that Smilacis Glabrae Rhizoma could alleviate oxidative stress by upregulating catalase. In vitro experiments, we found that high concentrations of uric acid reduced catalase expression in endothelial cells, which was alleviated by Smilacis Glabrae Rhizoma and resulted in a reduction of reactive oxygen species. Knockdown of catalase led to an increase in reactive oxygen species. Conclusion: We demonstrated that Smilacis Glabrae Rhizoma could alleviate the oxidative stress caused by hyperuricemia by upregulating catalase expression. This finding could represent a new application for Smilacis Glabrae Rhizoma in the treatment of hyperuricemia. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]