High Concentrations of Uric Acid Inhibit Endothelial Cell Migration via miR‐663 Which Regulates Phosphatase and Tensin Homolog by Targeting Transforming Growth Factor‐<i>β</i>1

Abstract

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.