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Jørgen Frøkiær

Disruption of cyclooxygenase-2 prevents downregulation of cortical AQP2 and AQP3 in response to bilateral ureteral obstruction in the mouse

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  • Line Nilsson, Denmark
  • Kirsten Morill Madsen, Radiation Research Division, Denmark
  • Sukru Oguzkan Topcu, Denmark
  • Linda Boye Jensen, Department of Micro- and Nanotechnology, Denmark
  • Jørgen Frøkiær
  • Rikke Nørregaard
Bilateral ureteral obstruction (BUO) in rats is associated with increased cyclooxygenase type 2 (COX-2) expression, and selective COX-2 inhibition prevents downregulation of aquaporins (AQPs) in response to BUO. It was hypothesized that a murine model would display similar changes in renal COX-2 and AQPs upon BUO and that targeted disruption of COX-2 protects against BUO-induced suppression of collecting duct AQPs. COX-2(-/-) and wild-type littermates (C57BL/6) were employed to determine COX-1, -2, AQP2, and AQP3 protein abundances and localization after BUO. In a separate series, sham and BUO wild-type mice were treated with a selective COX-2 inhibitor, parecoxib. The COX-2 protein level increased in wild-type mice in response to BUO and was not detectable in COX-2(-/-). COX-1 protein abundance was increased in sham-operated and BUO mice. Total AQP2 and -3 mRNA and protein levels decreased significantly after BUO in the cortex+outer medulla (C+OM) and inner medulla (IM). The decrease in C+OM AQP2 and -3 levels was attenuated/prevented in COX-2(-/-) mice, whereas there was no change in the IM. In parallel, inhibition of COX-2 by parecoxib rescued C+OM AQP3 and IM AQP2 protein level in wild-type mice subjected to BUO. In summary, 1) In C57BL/6 mice, ureteral obstruction increases renal COX-2 expression in interstitial cells and lowers AQP2/-3 abundance and 2) inhibition of COX-2 activity by targeted disruption or pharmacological blockade attenuates obstruction-induced AQP downregulation. In conclusion, COX-2-derived prostaglandins contribute to downregulation of transcellular water transporters in the collecting duct and likely to postobstruction diureses in the mouse.
Original languageEnglish
JournalAmerican Journal of Physiology: Renal Physiology
Volume302
Issue11
Pages (from-to)F1430-9
Number of pages10
ISSN1931-857X
DOIs
Publication statusPublished - 2012

    Research areas

  • Animals, Aquaporin 2, Aquaporin 3, Blotting, Western, Body Weight, Cyclooxygenase 2, Cyclooxygenase 2 Inhibitors, Down-Regulation, Electrophoresis, Polyacrylamide Gel, Immunohistochemistry, Isoxazoles, Kidney, Kidney Cortex, Mice, Mice, Inbred C57BL, Mice, Knockout, Organ Size, Polymerase Chain Reaction, RNA, Ureteral Obstruction

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