| The Effect of Monocyte Chemoattractant Protein-1 (MCP-1) on Epithelial-Mesenchymal Transition in Human Peritoneal Mesothelial Cells |
| Jin-Ji Li, M.D.1, Tae-Hyun Yoo, M.D.1, Shin-Wook Kang, M.D.1, Jung Min Lee, M.D.2, Jung-Hwa Ryu, M.D.2, Mina Yu, M.D.2 , Dong-Ryeol Ryu, M.D.2, Seung-Jung Kim, M.D.2, Duk-Hee Kang, M.D.2, Kyu Bok Choi, M.D.2 and Kyun Il Yoon, M.D.2 |
Department of Internal Medicine1
College of Medicine, Yonsei University, Department of Internal Medicine2
School of Medicine, Ewha Womans University, Seoul, Korea |
| 원저 : Monocyte Chemoattractant Protein-1 (MCP-1)이 인간 복막중피세포의 상피-중간엽 이행 (epithelial to mesenchymal transition)에 미치는 영향 |
| 이금희1, 유태현1, 강신욱1, 이정민2, 류정화2, 유민아2, 류동열2, 김승정2, 강덕희2, 최규복2, 윤견일2 |
| 연세대학교 의과대학 내과학교실1, 이화여자대학교 의학전문대학원 내과학교실2 |
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| Abstract |
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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 μM 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, α-smooth muscle actin (α-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. α-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.
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| Key Words:
Monocyte chemoattractant protein-1, CC chemokine receptor 2, Epithelial to mesenchymal transition, P |
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