PMID- 23007133
OWN - NLM
STAT- MEDLINE
DCOM- 20130415
LR  - 20230216
IS  - 1530-0307 (Electronic)
IS  - 0023-6837 (Linking)
VI  - 92
IP  - 12
DP  - 2012 Dec
TI  - The monocyte chemoattractant protein-1 (MCP-1)/CCR2 system is involved in 
      peritoneal dialysis-related epithelial-mesenchymal transition of peritoneal 
      mesothelial cells.
PG  - 1698-711
LID - 10.1038/labinvest.2012.132 [doi]
AB  - Epithelial-mesenchymal transition (EMT) of peritoneal mesothelial cells (PMCs) 
      has a role in the process of peritoneal fibrosis (PF), a serious complication in 
      peritoneal dialysis (PD) patients. Even though monocyte chemoattractant protein-1 
      (MCP-1) was demonstrated to directly increase extracellular matrix (ECM) 
      synthesis, the role of the MCP-1/CCR2 system in PD-related EMT and ECM synthesis 
      in cultured human PMCs (HPMCs) and in an animal model of PD has never been 
      elucidated. In vitro, HPMCs were exposed to 5.6 mM glucose (NG), NG+MCP-1 
      (10 ng/ml) (NG+MCP-1), or 100 mM glucose (HG) with or without CCR2 inhibitor 
      (RS102895) (CCR2i) or a dominant-negative mutant MCP-1-expressing lentivirus 
      (LV-mMCP-1). In vivo, PD catheters were inserted into 60 Sprague-Dawley rats, and 
      saline (Control, C) (N=30) or 4.25% PD solution (PD) (N=30) was infused for 4 
      weeks. Twenty rats from each group were treated with empty LV or LV-mMCP-1 
      intraperitoneally. Snail, E-cadherin, alpha-smooth muscle actin (alpha-SMA), and 
      fibronectin protein expression in HPMCs and the peritoneum was evaluated by 
      western blot analysis. Compared with NG cells, Snail, alpha-SMA, and fibronectin 
      expression was significantly increased, while E-cadherin expression was 
      significantly decreased in HPMCs exposed to HG and NG+MCP-1, and these changes 
      were significantly abrogated by CCR2i (P<0.05). In addition, MCP-1-induced EMT 
      was significantly attenuated by anti-TGF-beta1 antibody. In PD rats, Snail and 
      fibronectin expression was significantly increased in the peritoneum, whereas the 
      ratios of E-cadherin/alpha-SMA protein expression were significantly decreased 
      (P<0.05). The thickness of the peritoneum and the intensity of Masson's trichrome 
      staining in the peritoneum were also significantly higher in PD rats than in C 
      rats (P<0.05). These changes in PD rats were significantly abrogated by 
      LV-mMCP-1. These findings suggest that the MCP-1/CCR2 system is directly involved 
      in PD-related EMT and ECM synthesis and that this is mediated, at least in part, 
      via TGF-beta1.
FAU - Lee, Sun Ha
AU  - Lee SH
AD  - Department of Internal Medicine, College of Medicine, Brain Korea 21, Severance 
      Biomedical Science Institute, Yonsei University, Seoul, Korea.
FAU - Kang, Hye-Young
AU  - Kang HY
FAU - Kim, Kyung Sik
AU  - Kim KS
FAU - Nam, Bo Young
AU  - Nam BY
FAU - Paeng, Jisun
AU  - Paeng J
FAU - Kim, Seonghun
AU  - Kim S
FAU - Li, Jin Ji
AU  - Li JJ
FAU - Park, Jung Tak
AU  - Park JT
FAU - Kim, Dong Ki
AU  - Kim DK
FAU - Han, Seung Hyeok
AU  - Han SH
FAU - Yoo, Tae-Hyun
AU  - Yoo TH
FAU - Kang, Shin-Wook
AU  - Kang SW
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120924
PL  - United States
TA  - Lab Invest
JT  - Laboratory investigation; a journal of technical methods and pathology
JID - 0376617
RN  - 0 (CCR2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Fibronectins)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Transforming Growth Factor beta1)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Cells, Cultured
MH  - Chemokine CCL2/genetics/*metabolism
MH  - Epithelial Cells/cytology/*metabolism
MH  - Epithelial-Mesenchymal Transition/*physiology
MH  - Extracellular Matrix/metabolism
MH  - Fibronectins/metabolism
MH  - Glucose/metabolism
MH  - HEK293 Cells
MH  - Humans
MH  - Male
MH  - Peritoneal Dialysis/*adverse effects
MH  - Peritoneal Fibrosis/metabolism
MH  - Peritoneum/*cytology/pathology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, CCR2/*metabolism
MH  - Signal Transduction
MH  - Transforming Growth Factor beta1/metabolism
EDAT- 2012/09/26 06:00
MHDA- 2013/04/16 06:00
CRDT- 2012/09/26 06:00
PHST- 2012/09/26 06:00 [entrez]
PHST- 2012/09/26 06:00 [pubmed]
PHST- 2013/04/16 06:00 [medline]
AID - S0023-6837(22)01662-2 [pii]
AID - 10.1038/labinvest.2012.132 [doi]
PST - ppublish
SO  - Lab Invest. 2012 Dec;92(12):1698-711. doi: 10.1038/labinvest.2012.132. Epub 2012 
      Sep 24.