The Effect of Monocyte Chemoattractant Protein-1 (MCP-1) on Epithelial-Mesenchymal Transition in Human Peritoneal Mesothelial Cells / 대한신장학회지
Korean Journal of Nephrology
;
: 545-552, 2008.
Article
in Korean
| WPRIM
| ID: wpr-24730
ABSTRACT
PURPOSE:
This study was undertaken to elucidate whether CC chemokine receptor 2 (CCR2) exists in human peritoneal mesothelial cells (HPMCs) and whether monocyte chemoattractant protein-1 (MCP-1) has direct effects on epithelial to mesenchymal transition (EMT) and fibronectin expression in HPMCs.METHODS:
HPMCs were isolated from a piece of human omentum and were incubated with M199 media containing 5.6 mM glucose (LG), 5.6 mM glucose+94.4 mM mannitol (LG+M), LG+10 ng/mL recombinant human MCP-1 (LG+MCP-1), or 100 mM glucose (HG) with or without a specific inhibitor of CCR2, 1.0 micrometer RS102895, for 4 days. Levels of secreted MCP-1 in culture media were determined by ELISA. Western blot was performed to determine fibronectin, E-cadherin, alpha-smooth muscle actin (alpha-SMA) and CCR2 protein expression.RESULTS:
MCP-1 protein levels were significantly increased in HG-conditioned media compared to LG media (p<0.05). CCR2 protein was expressed in HPMCs, but there was no difference between LGand HG-stimulated cells. alpha-SMA protein expressions in HG and LG+MCP-1 groups were significantly higher relative to LG cells, while E-cadherin protein expressions were decreased in HG and LG+ MCP-1 groups compared to LG cells (p<0.05). In addition, there were significant increases in fibronectin mRNA and protein expression in HG and LG+MCP-1 groups (p<0.05). These HG-induced changes were significantly abrogated upon pre-treatment with RS102895.CONCLUSION:
HG and MCP-1 directly induce EMT and enhance fibronectin expression in HPMCs, and these HG-induced changes were attenuated by the inhibition of MCP-1/CCR2 system, suggesting that increased MCP-1 levels by HG may contribute to the development of peritoneal fibrosis.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Omentum
/
Peritoneum
/
RNA, Messenger
/
Enzyme-Linked Immunosorbent Assay
/
Monocytes
/
Cadherins
/
Blotting, Western
/
Actins
/
Fibronectins
/
Chemokine CCL2
Limits:
Humans
Language:
Korean
Journal:
Korean Journal of Nephrology
Year:
2008
Type:
Article
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