The restorative effect of a selective cyclooxygenase-2 inhibitor on urothelial cell-cell interactions after partial bladder outlet obstruction in rats.

OBJECTIVE

To determine the changes in cyclooxygenase-2 (COX-2), E-cadherin and alpha-catenin expression after partial bladder outlet obstruction (PBOO), and whether a selective COX-2 inhibitor (celecoxib) might inhibit COX-2 expression and have beneficial effects on urothelial cell-to-cell interactions in rats subjected to PBOO.

METHODS

Thirty-six male rats were divided into six equal groups; celecoxib was administered after creating PBOO for 1 and 4 weeks in groups 1 and 2, respectively. Two further obstructed groups (3 and 4, PBOO for 1 and 4 weeks, respectively) received no treatment. Sham-operated animals served as controls (group 5 and 6, assessed at 1 and 4 weeks, respectively). After 1 and 4 weeks of PBOO or a sham procedure the bladder weight was recorded before sampling the bladder for Western blotting and immunohistological analysis, to assess the expressions of COX-2 and adherens proteins, E-cadherin and alpha-catenin. Urothelial cell-to-cell interactions were evaluated using electron microscopy.

RESULTS

The bladder mass increased rapidly during the first 7 days after PBOO in groups 1-4 compared with 5 and 6 (P < 0.05). While the bladder mass then continued to increase for the next 21 days in group 4, it was constant in group 2 (P < 0.001). Immunohistochemical staining and Western blotting analyses showed that E-cadherin and alpha-catenin expression were reversibly decreased in rats with PBOO, while COX-2 protein expression was up-regulated. After giving celecoxib there was a significant decrease in COX-2 expression and a restoration of intercellular adherens junctions and desmosomes, as assessed on electron microscopy and expression of adherens proteins combined.

CONCLUSIONS

The increase in COX-2 expression attributable to hypoxia and the tensile strength of bladder wall was attenuated by celecoxib. Selective COX-2 inhibitors have important restorative effects on intercellular adherens junctions and desmosomes in PBOO.