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This Article Full Text Full Text (PDF) All Versions of this Article: 583/1/287    most recent jphysiol.2007.135178v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Neuhofer, W. Articles by Beck, F.-X Search for Related Content PubMed PubMed Citation Articles by Neuhofer, W. Articles by Beck, F.-X Related Collections Renal and Endocrine

¹ Department of Physiology, University of Munich, Munich, Germany

The cells of the renal medulla produce large amounts of prostaglandin E₂ (PGE₂) via cyclooxygenases (COX)-1 and -2. PGE₂ is well known to play a critical role in salt and water balance and maintenance of medullary blood flow. Since renal medullary PGE₂ production increases in antidiuresis, and since COX inhibition is associated with damage to the renal medulla during water deprivation, PGE₂ may promote the adaptation of renal papillary cells to high interstitial solute concentrations. To address this question, MDCK cells were exposed to a gradual tonicity increase in the presence or absence of 20 µM PGE₂ prior to analysis of (i) cell survival, (ii) expression of osmoprotective genes (AR, BGT1, SMIT, HSP70 and COX-2), (iii) subcellular TonEBP/NFAT5 abundance, (iv) TonEBP/NFAT5 transcriptional activity and (v) aldose reductase promoter activity. Cell survival and apoptotic indices after raising the medium tonicity improved markedly in the presence of PGE₂. PGE₂ significantly increased tonicity-mediated up-regulation of AR, SMIT and HSP70 mRNAs. However, neither nuclear abundance nor TonEBP/NFAT5-driven reporter activity were elevated by PGE₂, but aldose reductase promoter activity was significantly increased by PGE₂. Interestingly, tonicity-induced COX-2 expression and activity was also stimulated by PGE₂, suggesting the existence of a positive feedback loop. These results demonstrate that the major medullary prostanoid, PGE₂, stimulates the expression of osmoprotective genes and favours the adaptation of medullary cells to increasing interstitial tonicities, an effect that is not explained directly by the presence of TonEs in the promoter region of the respective target genes. These findings may be relevant in the pathophysiology of medullary damage associated with analgesic drugs.

(Received 24 April 2007; accepted after revision 6 June 2007; first published online 6 June 2007)
Corresponding author W. Neuhofer, Department of Physiology, University of Munich, Pettenkoferstrasse 12, 80336 Munich, Germany. Email: wolfgang.neuhofer{at}med.uni-muenchen.de

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