title: The restorative effect of a selective cyclooxygenase-2 inhibitor on urothelial cell-cell interactions after partial bladder outlet obstruction in rats.
abstract: 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.
authors.affiliation: Department of Urology, Akdeniz University Faculty of Medicine, Antalya, Turkey. terdogru@akdeniz.edu.tr
authors.forename: Tibet
authors.initials: T
authors.lastname: Erdogru
authors.forename: Ciler
authors.initials: C
authors.lastname: Celik-Ozenci
authors.forename: Yasemin
authors.initials: Y
authors.lastname: Seval
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Emreoglu
authors.forename: Ismail
authors.initials: I
authors.lastname: Ustunel
authors.forename: Emin
authors.initials: E
authors.lastname: Korgun
authors.forename: Turker I
authors.initials: TI
authors.lastname: Koksal
authors.forename: Mehmet
authors.initials: M
authors.lastname: Baykara
authors.forename: Ramazan
authors.initials: R
authors.lastname: Demir
mesh_terms: 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
chemical_list: D015820:Cadherins; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D003598:Cytoskeletal Proteins; D051178:alpha Catenin; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases