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NFAT5 Contributes to Osmolality-Induced MCP-1 Expression in Mesothelial Cells

Increased expression of the C-C chemokine monocyte chemoattractant protein-1 (MCP-1) in mesothelial cells in response to high glucose concentrations and/or high osmolality plays a crucial role in the development of peritoneal fibrosis during continuous ambulatory peritoneal dialysis (CAPD). Recent s...

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Detalles Bibliográficos
Autores principales: Küper, Christoph, Beck, Franz-X., Neuhofer, Wolfgang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3350971/
https://www.ncbi.nlm.nih.gov/pubmed/22619484
http://dx.doi.org/10.1155/2012/513015
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author Küper, Christoph
Beck, Franz-X.
Neuhofer, Wolfgang
author_facet Küper, Christoph
Beck, Franz-X.
Neuhofer, Wolfgang
author_sort Küper, Christoph
collection PubMed
description Increased expression of the C-C chemokine monocyte chemoattractant protein-1 (MCP-1) in mesothelial cells in response to high glucose concentrations and/or high osmolality plays a crucial role in the development of peritoneal fibrosis during continuous ambulatory peritoneal dialysis (CAPD). Recent studies suggest that in kidney cells osmolality-induced MCP-1 upregulation is mediated by the osmosensitive transcription factor, nuclear factor of activated T cells 5 (NFAT5). The present study addressed the question of whether activation of NFAT5 by hyperosmolality, as present in PD fluids, contributes to MCP-1 expression in the mesothelial cell line Met5A. Hyperosmolality, induced by addition of glucose, NaCl, or mannitol to the growth medium, increased NFAT5 activity and stimulated MCP-1 expression in Met5A cells. siRNA-mediated knockdown of NFAT5 attenuated osmolality-induced MCP-1 upregulation substantially. Hyperosmolality also induced activation of nuclear factor-κB (NF-κB). Accordingly, pharmacological inhibition of NF-κB significantly decreased osmolality-induced MCP-1 expression. Taken together, these results indicate that high osmolalities activate the transcription factor NFAT5 in mesothelial cells. NFAT5 in turn upregulates MCP-1, likely in combination with NF-κB, and thus may participate in the development of peritoneal fibrosis during CAPD.
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spelling pubmed-33509712012-05-22 NFAT5 Contributes to Osmolality-Induced MCP-1 Expression in Mesothelial Cells Küper, Christoph Beck, Franz-X. Neuhofer, Wolfgang Mediators Inflamm Research Article Increased expression of the C-C chemokine monocyte chemoattractant protein-1 (MCP-1) in mesothelial cells in response to high glucose concentrations and/or high osmolality plays a crucial role in the development of peritoneal fibrosis during continuous ambulatory peritoneal dialysis (CAPD). Recent studies suggest that in kidney cells osmolality-induced MCP-1 upregulation is mediated by the osmosensitive transcription factor, nuclear factor of activated T cells 5 (NFAT5). The present study addressed the question of whether activation of NFAT5 by hyperosmolality, as present in PD fluids, contributes to MCP-1 expression in the mesothelial cell line Met5A. Hyperosmolality, induced by addition of glucose, NaCl, or mannitol to the growth medium, increased NFAT5 activity and stimulated MCP-1 expression in Met5A cells. siRNA-mediated knockdown of NFAT5 attenuated osmolality-induced MCP-1 upregulation substantially. Hyperosmolality also induced activation of nuclear factor-κB (NF-κB). Accordingly, pharmacological inhibition of NF-κB significantly decreased osmolality-induced MCP-1 expression. Taken together, these results indicate that high osmolalities activate the transcription factor NFAT5 in mesothelial cells. NFAT5 in turn upregulates MCP-1, likely in combination with NF-κB, and thus may participate in the development of peritoneal fibrosis during CAPD. Hindawi Publishing Corporation 2012 2012-02-22 /pmc/articles/PMC3350971/ /pubmed/22619484 http://dx.doi.org/10.1155/2012/513015 Text en Copyright © 2012 Christoph Küper et al. https://creativecommons.org/licenses/by/3.0/ 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.
spellingShingle Research Article
Küper, Christoph
Beck, Franz-X.
Neuhofer, Wolfgang
NFAT5 Contributes to Osmolality-Induced MCP-1 Expression in Mesothelial Cells
title NFAT5 Contributes to Osmolality-Induced MCP-1 Expression in Mesothelial Cells
title_full NFAT5 Contributes to Osmolality-Induced MCP-1 Expression in Mesothelial Cells
title_fullStr NFAT5 Contributes to Osmolality-Induced MCP-1 Expression in Mesothelial Cells
title_full_unstemmed NFAT5 Contributes to Osmolality-Induced MCP-1 Expression in Mesothelial Cells
title_short NFAT5 Contributes to Osmolality-Induced MCP-1 Expression in Mesothelial Cells
title_sort nfat5 contributes to osmolality-induced mcp-1 expression in mesothelial cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3350971/
https://www.ncbi.nlm.nih.gov/pubmed/22619484
http://dx.doi.org/10.1155/2012/513015
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