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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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2012
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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. |
format | Online Article Text |
id | pubmed-3350971 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
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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