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Urinary tract obstruction induces time‐dependent COX‐2 induction and downregulation of AQP2
Author(s) -
Norregaard Rikke,
Madsen Tina,
Jensen Boye L.,
Nielsen Søren,
Frøkiær Jørgen
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1221
Subject(s) - downregulation and upregulation , immunohistochemistry , kidney , aquaporin 2 , endocrinology , medicine , urinary system , andrology , renal medulla , chemistry , gene , water channel , biochemistry , mechanical engineering , engineering , inlet
Bilateral ureteral obstruction (BUO) is associated with increased COX‐2 and decreased AQP2 expression in rat kidney inner medulla (IM). In this study we examined how rapidly the induction of COX‐2 and how rapidly the downregulation of AQP2 occur in IM during BUO. Rats were exposed to varying durations of BUO or sham operated. Rats were sacrificed 2, 6 12 and 24 hours after onset of BUO. The two kidneys were removed and separately prepared for semiquantitative immunoblotting. In a subset of animals kidneys were perfusion fixed for immunohistochemistry. COX‐1 expression was unchanged in IM at all time points. Semiquantitative immunoblotting showed no change in COX‐2 abundance at 2 and 6 h after onset of BUO, there was markedly increased in IM 12 h after onset of BUO (1±0.3 vs. 10.9±1.8, n=6, p<0.001). This level of COX‐2 expression was comparably with that observed after 24hBUO. Importantly, AQP2 expression was downregulated 12h after onset of BUO (1±0.1 vs. 0.68±0.1, n=6, p<0.05) and even further decreased after 24hBUO in IM (0.21±0.05 n=6, p<0.05). Immunohistochemistry confirmed these findings. These data indicate that BUO is associated with an early induction of COX‐2 in IM. This may contribute to the parallel decrease in AQP2 expression and thereby play a role in the altered renal tubular function in response to BUO.