title: High Concentrations of Uric Acid Inhibit Endothelial Cell Migration via miR-663 Which Regulates Phosphatase and Tensin Homolog by Targeting Transforming Growth Factor-β1.
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.
  
  
  CONCLUSIONS
  HUA inhibits endothelial cell migration via miR-663, which regulates PTEN by targeting TGF-β1.
authors: State Key Laboratory of Kidney Diseases, Department of Nephrology, National Clinical Research Center of Kidney Diseases, Chinese PLA Institute of Nephrology, Chinese PLA General Hospital, Beijing, China.
authors: Quan
authors: Q
authors: Hong
authors: Shandong
authors: S
authors: Yu
authors: Xiaodong
authors: X
authors: Geng
authors: Liping
authors: L
authors: Duan
authors: Wei
authors: W
authors: Zheng
authors: Men
authors: M
authors: Fan
authors: Xiangmei
authors: X
authors: Chen
authors: Di
authors: D
authors: Wu
mesh_terms: D000818:Animals; D002460:Cell Line; D002465:Cell Movement; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic; D033461:Hyperuricemia / Q000097:blood* / Q000473:pathology; D035683:MicroRNAs / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000096:biosynthesis*; D051381:Rats; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D014527:Uric Acid / Q000097:blood*; D014945:Wound Healing
chemical_list: D035683:MicroRNAs; C508962:Tgfb1 protein, rat; D053773:Transforming Growth Factor beta1; D014527:Uric Acid; D051059:PTEN Phosphohydrolase; C487216:Pten protein, rat
keywords: endothelial cell migration; microRNA-663; phosphatase and tensin homolog; transforming growth factor-β1; uric acid