The Effect of Monocyte Chemoattractant Protein-1 (MCP-1) on Epithelial-Mesenchymal Transition in Human Peritoneal Mesothelial Cells.
- Author:
Jin Ji LI
1
;
Tae Hyun YOO
;
Shin Wook KANG
;
Jung Min LEE
;
Jung Hwa RYU
;
Mina YU
;
Dong Ryeol RYU
;
Seung Jung KIM
;
Duk Hee KANG
;
Kyu Bok CHOI
;
Kyun Il YOON
Author Information
1. Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Korea.
- Publication Type:Original Article
- Keywords:
Monocyte chemoattractant protein-1;
CC chemokine receptor 2;
Epithelial to mesenchymal transition;
Peritoneum
- MeSH:
Actins;
Blotting, Western;
Cadherins;
Chemokine CCL2;
Culture Media;
Enzyme-Linked Immunosorbent Assay;
Epithelial-Mesenchymal Transition;
Fibronectins;
Glucose;
Humans;
Mannitol;
Monocytes;
Muscles;
Omentum;
Peritoneum;
Receptors, CCR2;
RNA, Messenger
- From:Korean Journal of Nephrology
2008;27(5):545-552
- CountryRepublic of Korea
- Language:Korean
-
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.
