Tristetraprolin regulates the decay of the hypoxia-induced vascular endothelial growth factor mRNA in ARPE-19 cells

Abstract

The aim of the present study was to investigate the effects of tristetraprolin (TTP) on the vascular endothelial growth factor (VEGF) mRNA and protein expression levels in retinal pigment epithelial cells under hypoxic conditions, and to consider the possibility of using TTP as a novel treatment tool for neovascular age-related macular degeneration (AMD). Overexpression of TTP reduced the expression and secretion levels of VEGF in ARPE-19 cells under hypoxic conditions. TTP destabilized the VEGF mRNA by binding to adenosine and uridine-rich elements regions in its 3'-untranslated region. Furthermore, conditioned medium (CM) from TTP-overexpressing ARPE-19 cells suppressed the tube formation in human umbilical vein endothelial cells compared with hypoxic CM. These findings indicate that regulation of TTP expression may be a promising therapeutic tool for neovascular AMD, however, further research is required.