Jørgen Frøkiær

Increased cyclooxygenase-2 expression and prostaglandin E2 production in pressurized renal medullary interstitial cells

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  • Inge Gram Carlsen, Denmark
  • Kaitlin E Donohue, United States
  • Anja M Jensen, Denmark
  • Angela L Selzer, United States
  • Jie Chen, United States
  • Dix P Poppas, United States
  • Diane Felsen, United States
  • Jørgen Frøkiær
  • Rikke Nørregaard
Renal medullary interstitial cells (RMICs) are subjected to osmotic, inflammatory and mechanical stress as a result of ureteral obstruction, which may influence the expression and activity of cyclooxygenase type 2 (COX-2). Inflammatory stress strongly induces COX-2 in RMIC. To explore the direct effect of mechanical stress on the expression and activity of COX-2, cultured RMIC were subjected to varying amounts of pressure over time using a novel pressure apparatus. COX-2 mRNA and protein were induced following 60 mmHg for 4 and 6h, respectively. COX-1 mRNA and protein levels were unchanged. Prostaglandin E(2) (PGE(2)) production in the RMIC was increased, when cells were subjected to pressure of 60 mm Hg for 6h, and prevented by a selective COX-2 inhibitor. Pharmacological inhibition indicating that pressure-induced COX-2 expression is dependent on p38 mitogen-activated protein kinase (MAPK), and biochemical knockdown experiments showed that NFkappaB might be involved in the COX-2 induction by pressure. Importantly, TUNEL and MTT assay studies showed that subjecting RMIC to 60 mmHg pressure for 6h does not affect cell viability, apoptosis, and proliferation. To further examine the regulation of COX-2 in vivo, rats were subjected to unilateral ureteral obstruction (UUO) for 6 and 12 h. COX-2 mRNA and protein level was increased in inner medulla (IM) in response to 6 and 12h UUO. COX-1 mRNA and protein levels were unchanged. These findings suggest that in vitro application of pressure recapitulates the effects on RMIC found after in vivo UUO. This directly implicates pressure as an important regulator of renal COX-2 expression.
Original languageEnglish
JournalAmerican Journal of Physiology: Regulatory, Integrative and Comparative Physiology
Publication statusPublished - 2010

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