The potential role of NFAT5 and osmolarity in peritoneal injury.
A rise in osmotic concentration (osmolarity) activates the transcription factor Nuclear Factor of Activated T Cells 5 (NFAT5, also known as Tonicity-responsive Enhancer Binding Protein, TonEBP). This is part of a regulatory mechanism of cells adjusting to environments of high osmolarity. Under physiological conditions these are particularly important in the kidney. Activation of NFAT5 results in the modulation of various genes including some which promote inflammation. The osmolarity increases in patients with renal failure. Additionally, in peritoneal dialysis the cells of the peritoneal cavity are repeatedly exposed to a rise and fall in osmotic concentrations. Here we review the current information about NFAT5 activation in uremic patients and patients on peritoneal dialysis. We suggest that high osmolarity promotes injury in the "uremic" milieu, which results in inflammation locally in the peritoneal membrane, but most likely also in the systemic circulation.
Division of Nephrology, University Hospital Zurich, 8091 Zurich, Switzerland ; Institute of Physiology and Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, 8057 Zurich, Switzerland.
Harald
H
Seeger
Division of Nephrology, Department of Internal Medicine, Robert-Bosch-Hospital, 70376 Stuttgart, Germany.
Daniel
D
Kitterer
Division of Nephrology, Department of Internal Medicine, Robert-Bosch-Hospital, 70376 Stuttgart, Germany.
Joerg
J
Latus
Division of Nephrology, Department of Internal Medicine, Robert-Bosch-Hospital, 70376 Stuttgart, Germany.
Mark Dominik
MD
Alscher
Division of Nephrology, Department of Internal Medicine, Robert-Bosch-Hospital, 70376 Stuttgart, Germany.
Niko
N
Braun
Division of Nephrology, University Hospital Zurich, 8091 Zurich, Switzerland ; Institute of Physiology and Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, 8057 Zurich, Switzerland.
Stephan
S
Segerer
D003198:Computer Simulation; D006801:Humans; D008954:Models, Biological; D009994:Osmolar Concentration; D009997:Osmotic Pressure; D010530:Peritoneal Dialysis / Q000009:adverse effects*; D056627:Peritoneal Fibrosis; D010537:Peritoneum / Q000503:physiopathology*; D014157:Transcription Factors / Q000378:metabolism*; D014511:Uremia / Q000150:complications / Q000628:therapy*
C118125:NFAT5 protein, human; D014157:Transcription Factors