Regulated Expression of PTPRJ by COX-2/PGE2 Axis in Endothelial Cells

• Published in: PloS one Vol. 9; no. 12; p. e114996
• 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: United States Public Library of Science 2014; Public Library of Science (PLoS)
• Subjects: Angiogenesis; Animals; Bioinformatics; Biology and Life Sciences; Breast cancer; Carotid arteries; Celecoxib; Cell adhesion & migration; Cells, Cultured; Correlation; Correlation coefficient; Correlation coefficients; COX-2 inhibitors; Cyclooxygenase 2 - genetics; Cyclooxygenase 2 - metabolism; Cyclooxygenase 2 Inhibitors - pharmacology; Cyclooxygenase-2; Disease Models, Animal; Endothelial cells; Endothelial Cells - cytology; Endothelial Cells - metabolism; Enzymes; Gastroenterology; Gene expression; Gene Expression Regulation - drug effects; Genetic Vectors - genetics; Genetic Vectors - metabolism; Genomes; Geriatrics; Hepatology; Hospitals; Human Umbilical Vein Endothelial Cells; Humans; Hyperplasia; Hyperplasia - metabolism; Hyperplasia - pathology; Injury prevention; Kinases; Laboratories; Male; Medicine and Health Sciences; Morphology; Overexpression; Phosphatase; Plasmids; Polymerase chain reaction; Prostaglandin E2; Proteins; Proteomics; Pyrazoles - pharmacology; Rabbits; Receptor-Like Protein Tyrosine Phosphatases, Class 3 - genetics; Receptor-Like Protein Tyrosine Phosphatases, Class 3 - metabolism; Regulators; RNA, Messenger - metabolism; Rodents; Signal transduction; Signaling; Sulfonamides - pharmacology; Transfection; Tumors; Vascular endothelial growth factor; Veins & arteries; Western blotting
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0114996

This study was designed to examine a novel role of COX-2/PGE2 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 µg/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 10 µmol/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. 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.