Regulated expression of PTPRJ by COX-2/ PGE² axis in endothelial cells

Background: This study was designed to examine a novel role of COX-2/PGE² signaling as a regulator of PTPRJ expression in endothelial cells.

Methods: A bioinformatics analysis of a whole genome array was carried out to search for regulators of PTPRJ expression in endothelial cells. PTPRJ expression was also measured in endothelial cells derived from a balloon injury-induced neointimal hyperplasia model in male New Zealand Rabbits. Changes in PTPRJ expression in HUVEC cells was examined by RT-PCR and western blotting after transfection of COX-2 plasmids or treatment with varying concentrations of a COX- 2 inhibitor.

Results: A significant correlation was] identified between COX-2 and PTPRJ in GSE39264 (Pearson correlation coefficient =-0.87; n=22; P<0.01, two-tailed). PTPRJ expression was reduced during the progression of neointimal hyperplasia after balloon injury, which correlated with an increase in COX-2 expression. In HUVECs, after transfection with 1 1μg/ml, 0.5 μg/ml, or 0.25 μg/ml COX-2 plasmids, PTPRJ protein expression was reduced to 0.60- (±0.08), 0.75- (±0.09), and 0.88- (±0.04) fold, respectively, while mRNA expression was reduced to 0.15- (±0.03), 0.26- (±0.05), and 0.47- (±0.09) fold, respectively. After treatment of HUVECs with 10μmol/L or 20 μmol/L celecoxib, the reduction in PTPRJ expression induced by COX-2 over-expression was not only rescued but in fact increased by 2.05-fold (±0.28) and 3.34-fold (±0.37), respectively, compared with control.

Conclusions: Our results suggest that COX-2/PGE2 signaling may function as a negative regulator of PTPRJ expression in endothelial cells both in vivo and vitro.