Evaluation of Urothelial Stretch-Induced Cyclooxygenase-2 Expression in a Mouse Ureteral Obstruction Model

Abstract

Prostanoids play a major role in the nociceptive response to ureteral obstruction. Cyclooxygenases (COXs) 1 and 2 catalyze the rate-limiting step in prostanoid synthesis; COX-2 is the more inducible isoform. Previous studies in human and animal models have shown that COX-2 is highly induced during ureteral obstruction. Our objective was to characterize acute COX-2 induction in a reproducible mouse model. Unilateral ureteral ligation was performed, and obstruction was maintained for 2, 4, 6, 8, or 12 hours. We evaluated COX-2 protein expression using Western immunoblotting, and found that ureteral obstruction induced COX-2 expression ninefold within 6 hours. This is the first report to characterize in vivo temporal stretch-induced COX-2 expression in a mouse model. This model will be critical for elucidation of COX-2 signaling pathways and may eventually help to identify novel therapeutic targets for treating ureteral obstruction.