Biomechanical regulation of cyclooxygenase-2 in the renal collecting duct.

Biomechanical regulation of cyclooxygenase-2 in the renal collecting duct. Am J Physiol Renal Physiol. 2013 Nov 13; Authors: Liu Y, Flores D, Carrisoza-Gaytan R, Rohatgi R Abstract High dietary sodium (Na), a feature of the western diet, requires the kidney to excrete ample Na to maintain homeostasis and prevent hypertension. High urinary flow rate, presumably, leads to an increase in fluid shear stress (FSS) and FSS-mediated release of prostaglandin E2 (PGE2) by the cortical collecting duct (CCD) that enhances renal Na excretion. The pathways by which tubular flow biomechanically regulates PGE2 release and, cyclooxygenase-2 (COX-2) expression is limited. We hypothesized that FSS, through stimulation of neutral-sphingomyelinase (N-SM) activity, enhances COX-2 expression to boost Na excretion. To test this, inner medullary CD3 (IMCD3) cells were exposed to FSS in vitro and mice were injected with isotonic saline in vivo to induce high tubular flow. In vitro, FSS induced N-SM activity and COX-2 protein expression in cells while inhibition of N-SM activity repressed FSS-induced COX-2 protein abundance. Moreover, the murine CCD expresses N-SM protein and, when mice are injected with isotonic saline to induce high tubular flow, renal immunodetectable COX-2 is induced. Urinary PGE2 (445±91 pg/ml vs. 205±14 pg/ml; p<0.05) and microdissected CCDs (135.8±21.7 vs. 65.8±11.0 pg/ml/mm CCD; p<0.05) from saline-injected mice generate more PGE2 tha...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research