Obstruction stimulates cyclooxygenase-2 expression in bladder smooth muscle cells via increased mechanical stretch. Park, John M., Tianxin Yang_, Lois J. Arend_, J[umlaut]urgen B. Schnermann, Craig A. Peters, Michael R. Freeman and Josephine P. Briggs__. *Department of Urology, Children's Hospital and Harvard Medical School, Boston, MA; Departments of _Medicine, _Pathology and **Physiology, University of Michigan Medical School, Ann Arbor, MI;, __NIDDK, National Institutes of Health, Bethesda, MD
APStracts 5:0181F, 1998.
Studies were performed to investigate the regulatory mechanism of bladder cyclooxygenase-2 (COX-2) expression after outlet obstruction. In situ hybridization of murine bladder tissues using COX-2 specific riboprobes demonstrated that COX-2 expression was induced predominantly in the bladder smooth muscle cells after outlet obstruction. To study the effect of increased mechanical stretch on COX isoform expression, cultured rat bladder smooth muscle cells were grown on silicone elastomer-bottomed plates coated with collagen type I and were subjected to continuous cycles of stretch/relaxation for variable duration. COX-1 mRNA levels did not change with stretch. COX-2 expression increased in a time-dependent manner after stretch, with maximal mRNA and protein levels occurring after 4 hours. PGE2 levels increased more than 40-fold in the culture media after stretch, consistent with increased cyclooxygenase activity, and this was reduced to near completion in the presence of a COX-2 inhibitor, NS398. Exposure to stretch over a 48-hour period induced a 4.7 +/- 0.6 fold increase in tritiated thymidine incorporation rate. This increase in DNA synthesis was markedly suppressed when the cells were stretched in the presence of NS398. We conclude that in bladder obstruction COX-2 activation occurs predominantly in the smooth muscle cells in response to mechanical stretch. Our findings also suggest that stretch-activated COX-2 expression may participate in bladder smooth muscle cell proliferation and thereby play a role in pathological bladder wall thickening after obstruction. 

Received 26 January 1998; accepted in final form 8 October 1998.
APS Manuscript Number F15-8.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 10 November 1998