18
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      The Potential Role of NFAT5 and Osmolarity in Peritoneal Injury

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          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.

          Related collections

          Most cited references40

          • Record: found
          • Abstract: found
          • Article: not found

          Morphologic changes in the peritoneal membrane of patients with renal disease.

          This study examined the morphologic features of the parietal peritoneal membranes of 130 patients undergoing peritoneal dialysis (PD) and compared them with the features of the peritoneal membranes of normal individuals, uremic predialysis patients, and patients undergoing hemodialysis. The median thickness of the submesothelial compact collagenous zone was 50 microm for normal subjects, 140 microm for uremic patients, 150 microm for patients undergoing hemodialysis, and 270 microm for patients undergoing PD (P 97 mo, 700 microm (n = 19)]. Vascular changes included progressive subendothelial hyalinization, with luminal narrowing or obliteration. These changes were absent in samples from normal subjects but were present in 28% of samples from uremic patients and 56% of biopsies from patients undergoing PD. In the PD group, the prevalence of vasculopathy increased significantly with therapy duration (P = 0.0001). The density of blood vessels per unit length of peritoneum was significantly higher for patients with membrane failure and was correlated with the degree of fibrosis (P = 0.01). For the first time, a comprehensive cross-sectional analysis of the morphologic changes in the peritoneal membranes of patients undergoing PD is provided. The infrequency of fibrosis in the absence of vasculopathy suggests that vasculopathy may predispose patients to the development of fibrosis. This study provides a sufficiently large cohort of samples to allow structure-function relationships to be established, as well as providing a repository of tissue for further studies.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The role of NFAT transcription factors in integrin-mediated carcinoma invasion.

            Integrins, receptors for extracellular matrix ligands, are critical regulators of the invasive phenotype. Specifically, the alpha(6)beta(4) integrin has been linked with epithelial cell motility, cellular survival and carcinoma invasion, hallmarks of metastatic tumours. Previous studies have also shown that antagonists of the NFAT (nuclear factor of activated T-cells) family of transcription factors exhibit strong anti-tumour-promoting activity. This suggests that NFAT may function in tumour metastasis. Here, we investigate the involvement of NFAT in promoting carcinoma invasion downstream of the alpha(6)beta(4) integrin. We provide evidence that both NFAT1, and the recently identified NFAT5 isoform, are expressed in invasive human ductal breast carcinomas and participate in promoting carcinoma invasion using cell lines derived from human breast and colon carcinomas. NFAT1 and NFAT5 activity correlates with the expression of the alpha(6)beta(4) integrin. In addition, the transcriptional activity of NFAT5 is induced by alpha(6)beta(4) clustering in the presence of chemo-attractants, resulting in enhanced cell migration. These observations show that NFATs are targets of alpha(6)beta(4) integrin signalling and are involved in promoting carcinoma invasion, highlighting a novel function for this family of transcription factors in human cancer.
              Bookmark
              • Record: found
              • Abstract: not found
              • Article: not found

              Uremia.

                Bookmark

                Author and article information

                Journal
                Biomed Res Int
                Biomed Res Int
                BMRI
                BioMed Research International
                Hindawi Publishing Corporation
                2314-6133
                2314-6141
                2015
                30 September 2015
                : 2015
                : 578453
                Affiliations
                1Division of Nephrology, University Hospital Zurich, 8091 Zurich, Switzerland
                2Institute of Physiology and Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, 8057 Zurich, Switzerland
                3Division of Nephrology, Department of Internal Medicine, Robert-Bosch-Hospital, 70376 Stuttgart, Germany
                Author notes

                Academic Editor: Donald Fraser

                Article
                10.1155/2015/578453
                4606082
                396a99a1-18c6-48d4-8a80-b3f08a0b530d
                Copyright © 2015 Harald Seeger et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 9 June 2015
                : 12 July 2015
                Categories
                Review Article

                Comments

                Comment on this article