title: Activation of nuclear factor of activated T cells 5 in the peritoneal membrane of uremic patients.
abstract: Peritoneal inflammation and fibrosis are responses to the uremic milieu and exposure to hyperosmolar dialysis fluids in patients on peritoneal dialysis. Cells respond to high osmolarity via the transcription factor nuclear factor of activated T cells (NFAT5). In the present study, the response of human peritoneal fibroblasts to glucose was analyzed in vitro. Expression levels of NFAT5 and chemokine (C-C motif) ligand (CCL2) mRNA were quantified in peritoneal biopsies of five nonuremic control patients, five uremic patients before PD (pPD), and eight patients on PD (oPD) using real-time PCR. Biopsies from 5 control patients, 25 pPD patients, and 25 oPD patients were investigated using immunohistochemistry to detect the expression of NFAT5, CCL2, NF-κB p50, NF-κB p65, and CD68. High glucose concentrations led to an early, dose-dependent induction of NFAT5 mRNA in human peritoneal fibroblasts. CCL2 mRNA expression was upregulated by high concentrations of glucose after 6 h, but, most notably, a concentration-dependent induction of CCL2 was present after 96 h. In human peritoneal biopsies, NFAT5 mRNA levels were increased in uremic patients compared with nonuremic control patients. No significant difference was found between the pPD group and oPD group. CCL2 mRNA expression was higher in the oPD group. Immunohistochemistry analysis was consistent with the results of mRNA analysis. CD68-positive cells were significantly increased in the oPD group. In conclusion, uremia results in NFAT5 induction, which might promote early changes of the peritoneum. Upregulation of NFAT5 in PD patients is associated with NFκB induction, potentially resulting in the recruitment of macrophages.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Robert-Bosch-Hospital, Stuttgart, Germany;
authors.forename: Daniel
authors.initials: D
authors.lastname: Kitterer
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Robert-Bosch-Hospital, Stuttgart, Germany;
authors.forename: Joerg
authors.initials: J
authors.lastname: Latus
authors.affiliation: Department of General, Visceral, and Trauma Surgery, Robert-Bosch-Hospital, Stuttgart, Germany;
authors.forename: Christoph
authors.initials: C
authors.lastname: Ulmer
authors.affiliation: Department of Diagnostic Medicine, Division of Pathology, Robert-Bosch Hospital, Stuttgart, Germany;
authors.forename: Peter
authors.initials: P
authors.lastname: Fritz
authors.affiliation: Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, University of Tuebingen, Stuttgart, Germany;
authors.forename: Dagmar
authors.initials: D
authors.lastname: Biegger
authors.affiliation: Department of Diagnostic Medicine, Division of Pathology, Robert-Bosch Hospital, Stuttgart, Germany;
authors.forename: German
authors.initials: G
authors.lastname: Ott
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Robert-Bosch-Hospital, Stuttgart, Germany;
authors.forename: M Dominik
authors.initials: MD
authors.lastname: Alscher
authors.affiliation: Department of Pathophysiology, University of Medical Sciences, Poznan, Poland;
authors.forename: Janusz
authors.initials: J
authors.lastname: Witowski
authors.affiliation: Department of Nephrology and Medical Intensive Care, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany;
authors.forename: Edyta
authors.initials: E
authors.lastname: Kawka
authors.affiliation: Department of Nephrology and Medical Intensive Care, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany;
authors.forename: Achim
authors.initials: A
authors.lastname: Jörres
authors.affiliation: Division of Nephrology, University Hospital Zurich, Zurich, Switzerland; and Institute of Physiology and Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland.
authors.forename: Harald
authors.initials: H
authors.lastname: Seeger
authors.affiliation: Division of Nephrology, University Hospital Zurich, Zurich, Switzerland; and Institute of Physiology and Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland.
authors.forename: Stephan
authors.initials: S
authors.lastname: Segerer
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Robert-Bosch-Hospital, Stuttgart, Germany; braunniko@hotmail.com.
authors.forename: Niko
authors.initials: N
authors.lastname: Braun
mesh_terms: D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D018925:Chemokines / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D010530:Peritoneal Dialysis / Q000379:methods; D010537:Peritoneum / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation / Q000502:physiology; D014511:Uremia / Q000378:metabolism*
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D018925:Chemokines; D016328:NF-kappa B; C118125:NFAT5 protein, human; D014157:Transcription Factors; D005947:Glucose
keywords: chemokine (C-C motif) ligand 2; human peritoneal fibroblasts; mesothelial cell; monocyte chemoattractant protein-1; nuclear factor of activated T cells 5