PMID- 22619484
OWN - NLM
STAT- MEDLINE
DCOM- 20120920
LR  - 20211021
IS  - 1466-1861 (Electronic)
IS  - 0962-9351 (Print)
IS  - 0962-9351 (Linking)
VI  - 2012
DP  - 2012
TI  - NFAT5 contributes to osmolality-induced MCP-1 expression in mesothelial cells.
PG  - 513015
LID - 10.1155/2012/513015 [doi]
LID - 513015
AB  - 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-kappaB (NF-kappaB). Accordingly, pharmacological inhibition 
      of NF-kappaB 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-kappaB, and thus may participate in the development of 
      peritoneal fibrosis during CAPD.
FAU - Kuper, Christoph
AU  - Kuper C
AD  - Department of Physiology, University of Munich, 80336 Munich, Germany. 
      christoph.kueper@lrz.uni-muenchen.de
FAU - Beck, Franz-X
AU  - Beck FX
FAU - Neuhofer, Wolfgang
AU  - Neuhofer W
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120222
PL  - United States
TA  - Mediators Inflamm
JT  - Mediators of inflammation
JID - 9209001
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (NF-kappa B)
RN  - 0 (NFAT5 protein, human)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Cell Line
MH  - Chemokine CCL2/*biosynthesis
MH  - Epithelial Cells/cytology
MH  - Epithelium/*metabolism
MH  - *Gene Expression Regulation
MH  - Genes, Reporter
MH  - Humans
MH  - Kidney/metabolism
MH  - NF-kappa B/metabolism
MH  - Osmolar Concentration
MH  - Peritoneal Dialysis, Continuous Ambulatory/methods
MH  - Transcription Factors/*biosynthesis/metabolism
MH  - Transcriptional Activation
PMC - PMC3350971
EDAT- 2012/05/24 06:00
MHDA- 2012/09/21 06:00
PMCR- 2012/02/22
CRDT- 2012/05/24 06:00
PHST- 2011/12/21 00:00 [received]
PHST- 2012/01/28 00:00 [accepted]
PHST- 2012/05/24 06:00 [entrez]
PHST- 2012/05/24 06:00 [pubmed]
PHST- 2012/09/21 06:00 [medline]
PHST- 2012/02/22 00:00 [pmc-release]
AID - 10.1155/2012/513015 [doi]
PST - ppublish
SO  - Mediators Inflamm. 2012;2012:513015. doi: 10.1155/2012/513015. Epub 2012 Feb 22.