Sequential and synchronized hypertonicity-induced activation of Rel-family transcription factors is required for osmoprotection in renal cells

Abstract

NF-κB and TonEBP belong to the Rel-superfamily of transcription factors. Several specific stimuli, including hypertonicity which is a key factor for renal physiology, are able to activate them. It has been reported that, after hypertonic challenge, NF-κB activity can be modulated by TonEBP, considered as the master regulator of transcriptional activity in the presence of changes in environmental tonicity. In the present work we evaluated whether hypertonicity-induced gene transcription mediated by p65/RelA and TonEBP occurs by an independent action of each transcription factor or by acting together. To do this, we evaluated the expression of their specific target genes and cyclooxygenase-2 (COX-2), a common target of both transcription factors, in the renal epithelial cell line Madin-Darby canine kidney (MDCK) subjected to hypertonic environment. The results herein indicate that hypertonicity activates the Rel-family transcription factors p65/RelA and TonEBP in MDCK cells, and that both are required for hypertonic induction of COX-2 and of their specific target genes. In addition, present data show that p65/RelA modulates TonEBP expression and both colocalize in nuclei of hypertonic cultures of MDCK cells. Thus, a sequential and synchronized action p65/RelA → TonEBP would be necessary for the expression of hypertonicity-induced protective genes.

Cytosolic phospholipase A2 regulates lipid homeostasis under osmotic stress through PPARγ

“…Herein, we showed that hyperotonicity stimulates the incorporation of AA into GP (Figs 1 and 7) as well as cPLA2 expression (Figs 4 and 5). Whether hyperosmolality increased levels of cPLA 2 is now being studying in our lab but considering that cPLA 2 gene possess a kB‐response element in its regulatory regions [51,52] and that we showed that hyperosmolality activates NF‐kB [53], we can hypothesize that this transcription factor is responsible for cPLA 2 upregulation. In renal tissue and MDCKs cells subjected to hyperosmolality PLC activity, which increases cytosolic Ca 2+ concentration, modulates GP de novo synthesis [13,30].…”

Change in Metabolomic Profile Associated with an Average Increase in Plain Water Intake of >+1 L/Day, Sustained Over 4 Weeks, in Healthy Young Men with Initial Total Water Intake Below 2 L/Day

“…Cells respond to any deviation of the osmotic equilibrium between the intracellular and extracellular space with an obligated flux of water towards the compartment with the higher osmotic activity. The resulting alterations of cell volume, tension of the plasma and organellar membranes, ionic strength, and molecule concentrations elicit mechanotransduction and osmotic sensing which affect a wide range of cell processes and functions, including gene expression [17,18], cell proliferation, transport, metabolism, autophagy, redox-balance, fluid homeostasis, solute uptake, cell motility and migration, immune function, and programmed cell death [11,12,[19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34]. Sophisticated regulatory mechanisms precisely adjust cell volume, hydration, and metabolism [11,29,[35][36][37][38].…”

Bioavailable wine pomace attenuates oxalate-induced type II epithelial mesenchymal transition and preserve the differentiated phenotype of renal MDCK cells

“…Under the conditions of an abrupt change in osmolarity, renal cells activate various osmoprotective mechanisms to adapt for survival. Osmoprotective mechanisms include the expression of diverse osmoprotective proteins, actin cytoskeleton reorganization, vimentin modification, cytokeratin expression (Casali et al, 2018;Buchmaier et al, 2013), and the metabolic upregulation of phospholipids and triglycerides (Weber et al, 2018). All these changes contribute to preserve renal structure and function.…”