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.
Erdogru
Tibet
T
Department of Urology, Akdeniz University Faculty of Medicine, Antalya, Turkey. terdogru@akdeniz.edu.tr
Celik-Ozenci
Ciler
C
Seval
Yasemin
Y
Emreoglu
Ibrahim
I
Ustunel
Ismail
I
Korgun
Emin
E
Koksal
Turker I
TI
Baykara
Mehmet
M
Demir
Ramazan
R
D000818:Animals; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism; D002450:Cell Communication / Q000187:drug effects; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D008297:Male; D008854:Microscopy, Electron; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D001748:Urinary Bladder Neck Obstruction / Q000378:metabolism*; D051178:alpha Catenin
D015820:Cadherins; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D003598:Cytoskeletal Proteins; D051178:alpha Catenin; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases