Obstruction stimulates COX-2 expression in bladder smooth muscle cells via increased mechanical stretch

John M. Park, Tianxin Yang, Lois J. Arend, Jürgen B. Schnermann, Craig A. Peters, Michael R. Freeman, Josephine P. Briggs
1999 AJP - Renal Physiology  
Obstruction stimulates COX-2 expression in bladder smooth muscle cells via increased mechanical stretch. Am. J. Physiol. 276 (Renal Physiol. 45): F129-F136, 1999.-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
more » ... To study the effect of increased mechanical stretch on COX isoform expression, cultured rat bladder smooth muscle cells were grown on silicone elastomerbottomed 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 h. PGE 2 levels increased more than 40-fold in the culture media after stretch, consistent with increased COX activity, and this was reduced to near completion in the presence of a COX-2 inhibitor, NS-398. Exposure to stretch over a 48-h period induced a 4.7 Ϯ 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 NS-398. 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.
doi:10.1152/ajprenal.1999.276.1.f129 fatcat:dndxyfq5abde5k5fh3y75buqpy