Hypertonic induction of COX2 expression requires TonEBP/NFAT5 in renal epithelial cells

Biochemical and Biophysical Research Communications
N O FavaleM C Fernández-Tome

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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Citations

Dec 28, 2012·Journal of Lipid Research·Cecilia I CasaliMaría C Fernández Tome
May 1, 2015·Journal of Translational Medicine·Andrea RemoMichele Ceccarelli
Oct 11, 2011·Biochemical and Biophysical Research Communications·Yi-Hong HsinTsug-Han Lee
Nov 2, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Caroline ArnoldThomas Korff
Aug 4, 2020·Frontiers in Neuroscience·Arti TyagiNitesh Kumar Poddar
May 14, 2014·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Pankaj GargJong Hoon Chung
Jul 8, 2020·Journal of Orofacial Orthopedics = Fortschritte Der Kieferorthopädie : Organ/official Journal Deutsche Gesellschaft Für Kieferorthopädie·Agnes SchröderChristian Kirschneck
Dec 19, 2020·International Journal of Molecular Sciences·Christian KirschneckAgnes Schröder
Jan 14, 2020·Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids·Cecilia CasaliMaría C Fernández Tome
Jun 3, 2021·International Journal of Molecular Sciences·Guangze ZhaoDecheng Yang
Nov 6, 2018·Developmental Neuroscience·Xing-Liang YangBi-Wen Peng

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