Hypertonicity induces opposite regulation of PPARgamma and cyclooxygenase2 expression in renal cells

CASALI, CECILIA IRENE; WEBER, KAREN; MIKKELSEN, EVELYN; . FERNÁNDEZ TOME, MARIA DEL CARMEN

Congreso; XLVI Reunión de la Sociedad Argentina de Investigaciones Bioquímicas y Biología Molecular- SAIB; 2010

Peroxisome proliferator-activated receptors (PPARs) regulate the transcription of lipid metabolism related-genes including cyclooxygenase (COX2) which is considered an osmoprotective molecule in renal cells. Although PPARγ was demonstrated to be present in renal cells, the relationship between both proteins has not been established. The present work explores whether PPARγ regulates COX2 expression in renal epithelial cells in isotonic and hypertonic conditions. MDCK cell cultures were grown in isotonic (298 mOsm/Kg H2O) and NaCl-hypertonic (500 mOsm/Kg H2O) media in the absence or presence of PPARγ agonists, rosiglitazone (Rosi) and 15-deoxy-Δ12,14-PGJ2 (PGJ2), or antagonist, GW9662 (GW). After 24 h, treated cells were collected and submitted to westernblot analysis for PPARγ and COX2 In parallel experiments, immunofluorescence microscopy was performed. In isotonicity, Rosi and PGJ2 decreased COX2 expression, but they did not affect PPARγ protein. Therefore, the activation of PPARγ represses COX2 expression. In hypertonicity, the NaCl-induced increase of COX2 level was not prevented by GW, suggesting that PPARγ is not involved. But, when PPARγ was evaluated, the active form of PPARγ2 was withdrawn. Taken together these results suggest that the up-regulation of the osmoprotective gene COX2 in cells submitted to high-NaCl medium only occurs after the down-regulation of PPARγ2.