Increased COX‐2 expression and PGE2 production in pressurized renal medullary interstitial cells

Abstract

Pressure plays an important role during many physiological processes, and abnormal pressures may induce changes which favour onset and progression of disease in many organs. In vivo, renal medullary interstitial cells (RMIC) are subjected to pressure as a result of ureteral obstruction, which may influence the expression of COX‐2.To further examine this regulation, rats were subjected to unilateral ureteral obstruction (UUO) for 6 and 12h; showed increased COX‐2 mRNA levels in IM, whereas COX‐2 protein expression was increased only after 12hUUO. COX‐1 mRNA and protein level were unchanged. To explore the direct effect of pressure on the expression and activity of COX‐2 cultured RMIC were subjected to pressures of 60 mmHg over time (2‐12 h) using a novel pressure apparatus. QPCR confirmed increased COX‐2 mRNA after 2h. COX‐2 protein expression was increased following 60 mmHg of pressure for 6h. COX‐1 mRNA and protein levels were unchanged. PGE2 excretion from the RMIC was increased, when cells were subjected to pressure of 60 mm Hg for 6h, which was prevented by a selective COX‐2 inhibitor. Importantly, TUNEL and MTT assay studies showed that applying pressure to the RMIC does not affect cell viability, apoptosis, and proliferation.We demonstrated that in vitro application of pressure recapitulates the effects on RMIC found after in vivo UUO. This directly implicates pressure as an important regulator of renal COX‐2.