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Updated: Jun 26, 2026

Modeling Hypoxia/Reoxygenation Injury in Proximal Tubular Epithelial Cells
Published on: November 21, 2025
Hypertonic induction of COX2 expression requires TonEBP/NFAT5 in renal epithelial cells
N O Favale1, C I Casali, L G Lepera
1Department of Biological Sciences, School of Pharmacy and Biochemistry, University of Buenos Aires, IQUIFIB-CONICET, Ciudad Autónoma de Buenos Aires, Junín 956, 1er piso, (C1113AAD), Argentina.
Abstract:
TonEBP/NFAT5 transcription factor is a master regulator of genes involved in osmoprotection. Cyclooxygenase 2 (COX2) has been reported to be a cytoprotective molecule in the inner renal medulla, where cells are physiologically exposed to the highest osmolality of the body. Our aim was to study whether COX2 expression requires TonEBP/NFAT5. Incubation of MDCK cells in hypertonic NaCl medium (500 mOsm/kg H2O) caused fully translocation of TonEBP/NFAT5 from cytoplasm to nucleoplasm and significantly increased COX2 mRNA, protein and activity levels. TonEBP/NFAT5-siRNA prevented hypertonic induction of COX2 mRNA and protein, leading to a depressed-prostaglandin synthesis and to a decreased cell survival. By using COX2-siRNA and COX2 specific inhibitor NS398, we found that cell survival does not depend on endogenous COX2-induced prostaglandin synthesis, but that cytoprotection strongly correlates with COX2 protein levels. These results demonstrate a new function for TonEBP/NFAT5, i.e., to mediate hypertonic-induced COX2 expression, and suggest that osmoprotection strongly depends on COX2 protein levels.
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