Regulated Expression of PTPRJ by COX-2/PGE.sub.2 Axis in Endothelial Cells

• Published in: PloS one Vol. 9; no. 12
• Main Authors: Xu, Xiaobing, Lan, Wenya, Jin, Xinxin, Wang, Bin, Yan, Hongbo, Chen, Xi, Lai, Xiaowei, Zhang, Li, Zhang, Xiaohua, Li, Zhaoshen
• Format: Journal Article
• Language: English
• Published: Public Library of Science 22.12.2014
• Subjects: COX-2 inhibitors; Endothelium; Genomics; Infection; RNA
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0114996

This study was designed to examine a novel role of COX-2/PGE.sub.2 signaling as a regulator of PTPRJ expression in endothelial cells. 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. 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 [micro]g/ml, 0.5 [micro]g/ml, or 0.25 [micro]g/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 10 [micro]mol/L or 20 [micro]mol/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. 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.