Triptolide inhibits vascular endothelial growth factor expression and production in endothelial cells
Abstract
Aim: To investigate the effects of triptolide on vascular endothelial growth factor (VEGF) expression and secretion by endothelial cells, and explore the mechanism of anti-proteinuric effect of triptolide on glomerulonephritis.
Methods: A human umbilical endothelium derived cell line (ECV-304) from American Type Culture Collection (ATCC) was used in this study. The effects of triptolide on VEGF mRNA expression, production, and secretion induced by 12-o-tetradecanoyl-phorbol-13-acetate (TPA) were measured by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), flow cytometry, and enzyme linked immunosorbent assay (ELISA) respectively. The endothelial c-fos/c-jun mRNA expression were also detected by RT-PCR after treatment of triptolide.
Results: VEGF mRNA expression was markedly up-regulated by TPA-stimulation. In addition, the production and secretion of VEGF in endothelial cells also increased in TPA treated cells. It was founded that triptolide inhibited VEGF mRNA expression, protein production and secretion in endothelial cells induced by TPA. Interestingly, TPA-induced c-fos/c-jun mRNA expression in endothelial cells was also inhibited by triptolide.
Conclusion: Triptolide is a potent inhibitor of VEGF expression and production in endothelial cells. The inhibitory effects of triptolide on VEGF expression and production can contribute to its anti-proteinuric effect on glomerulonephritis. Down-regulation of c-fos/c-jun expression in endothelial cells by triptolide is one of the mechanisms of the inhibitory effect of triptolide on VEGF expression.
Keywords:
Methods: A human umbilical endothelium derived cell line (ECV-304) from American Type Culture Collection (ATCC) was used in this study. The effects of triptolide on VEGF mRNA expression, production, and secretion induced by 12-o-tetradecanoyl-phorbol-13-acetate (TPA) were measured by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), flow cytometry, and enzyme linked immunosorbent assay (ELISA) respectively. The endothelial c-fos/c-jun mRNA expression were also detected by RT-PCR after treatment of triptolide.
Results: VEGF mRNA expression was markedly up-regulated by TPA-stimulation. In addition, the production and secretion of VEGF in endothelial cells also increased in TPA treated cells. It was founded that triptolide inhibited VEGF mRNA expression, protein production and secretion in endothelial cells induced by TPA. Interestingly, TPA-induced c-fos/c-jun mRNA expression in endothelial cells was also inhibited by triptolide.
Conclusion: Triptolide is a potent inhibitor of VEGF expression and production in endothelial cells. The inhibitory effects of triptolide on VEGF expression and production can contribute to its anti-proteinuric effect on glomerulonephritis. Down-regulation of c-fos/c-jun expression in endothelial cells by triptolide is one of the mechanisms of the inhibitory effect of triptolide on VEGF expression.