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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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2012/513015 |
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| author | Christoph Küper Franz-X. Beck Wolfgang Neuhofer |
| author_facet | Christoph Küper Franz-X. Beck Wolfgang Neuhofer |
| author_sort | Christoph Küper |
| collection | DOAJ |
| 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 | Article |
| id | doaj-art-05e1123ad7714effa9d7f100c2194d1a |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-05e1123ad7714effa9d7f100c2194d1a2025-02-03T01:00:53ZengWileyMediators of Inflammation0962-93511466-18612012-01-01201210.1155/2012/513015513015NFAT5 Contributes to Osmolality-Induced MCP-1 Expression in Mesothelial CellsChristoph Küper0Franz-X. Beck1Wolfgang Neuhofer2Department of Physiology, University of Munich, 80336 Munich, GermanyDepartment of Physiology, University of Munich, 80336 Munich, GermanyDepartment of Physiology, University of Munich, 80336 Munich, GermanyIncreased 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.http://dx.doi.org/10.1155/2012/513015 |
| spellingShingle | Christoph Küper Franz-X. Beck Wolfgang Neuhofer NFAT5 Contributes to Osmolality-Induced MCP-1 Expression in Mesothelial Cells Mediators of Inflammation |
| 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 |
| url | http://dx.doi.org/10.1155/2012/513015 |
| work_keys_str_mv | AT christophkuper nfat5contributestoosmolalityinducedmcp1expressioninmesothelialcells AT franzxbeck nfat5contributestoosmolalityinducedmcp1expressioninmesothelialcells AT wolfgangneuhofer nfat5contributestoosmolalityinducedmcp1expressioninmesothelialcells |