Hypertonicity- induced PPARã2 downregulation is necessary for COX2 expression in renal medullary cells.

CASALI, CECILIA IRENE; WEBER, KAREN; FERNANDEZ TOME, MARIA DEL CARMEN

BILBAO

Congreso; INTERNATIONAL CONFERENCE ON THE BIOSCIENCE OF LIPIDS; 2010

icbl

Renal medullary cells are normally exposed to variable and high concentrations of NaCl as part of the urinary concentrating system. Despite such adverse conditions, renal cells still survive and function by activating the transcription of various osmoprotective genes, among them, cyclooxygenase 2 (COX2). Peroxisome proliferator-activated receptors (PPARs) are ligand-activated nuclear receptors that regulate the transcription of genes related to lipid metabolism that includes COX2 in different tissues. The presence of PPARã was also demonstrated in renal cells but the relationship between both proteins has not been established. The present work studies whether PPARã is involved in hypertonic COX2 up-regulation in renal cells. For this purpose, confluent cultures of MDCK cells were grown in isotonic (298 mOsm/Kg H2O) and NaCl-hypertonic (500 mOsm/Kg H2O) media in the absence or presence of PPARã agonists, rosiglitazone (Rosi) and 15-deoxy-Ä12,14-PGJ2 (PGJ2), or antagonist, GW9662 (GW). After 24 h, treated cells were submitted to westernblot analysis, and PPARã and COX2 protein expression was evaluated. In isotonicity, both Rosi and PGJ2 decreased COX2 expression; such effect was prevented by GW. No changes in PPARã were detected. Thus, in isotonicity, PPARã activation represses COX2 expression. In hypertonicity, NaCl increased-COX2 expression was not prevented by GW, suggesting that PPARã is not involved. When PPARã was evaluated, the active form of PPARã2 was clearly decreased. These results suggest that renal cells submitted to hypertonic stress need to withdraw PPARã 2 to ensure the expression of the osmoprotective gene COX2.