PMID- 18581895
OWN - NLM
STAT- MEDLINE
DCOM- 20081222
LR  - 20080627
IS  - 0376-2491 (Print)
IS  - 0376-2491 (Linking)
VI  - 88
IP  - 6
DP  - 2008 Feb 5
TI  - [Effects of induction of tubular epithelial-myofibroblast transition by monocyte 
      chemoattractant protein-1 and mechanism thereof: an in vitro experiment].
PG  - 400-5
AB  - OBJECTIVE: To examine the effects of monocyte chemoattractant protein-1 (MCP-1) 
      on epithelial-myofibroblast transition (EMT) of renal proximal tubular epithelial 
      cells and the possible mechanism involved. METHODS: Human renal proximal tubular 
      epithelial cells of the line HK-2 were cultured and divided into three groups: 
      negative control group; positive control group, treated with transforming growth 
      factor (TGF)-beta1 5 microg/L, and MPC-1 group, treated with MCP-1 0.1, 1, 10, 
      and 100 microg/L for 24 h, 36 h, 48 h, and 72 h respectively. The expressions of 
      alpha-smooth muscle actin (alpha-SMA) mRNA and protein of cells were detected by 
      s. Western blotting and RT-PCR were used to detect the expression of P-Erk1/2, 
      Erk1/2, P-P38MAPK, P38MAPK, and RhoA protein levels of the HK-2 cells, and RT-PCR 
      was used to detect the expression of RhoC and Snail mRNA. Specific inhibitors of 
      the Erk, P38MAPK, and Rho signal transduction pathways PD98059, SB203580, and 
      Y27632 were added into the culture fluid of HK-2 cells respectively, 1 h later 
      MCP-1 microg/L was added for 48 h, and Western blotting was used to detect the 
      protein expression of alpha-small muscle actin (SMA). RESULTS: The expression 
      levels of alpha-SMA protein and mRNA significantly increased in the MCP-1 treated 
      HK-2 cells,and these expression levels were the highest in the HK-2 cells treated 
      with MCP-1 1 microg/L for 48 h. The ratios of (P-Erk1/2)/ (Erk1/2) and 
      P-P38MAPK/P38MAPK were significantly increased (all P < 0.05) in the MCP-1 
      treated HK-2 cells with the highest ratios seen in the HK-2 cells treated by 100 
      microg/L of MCP-1. The expression levels of RhoA protein and RhoC mRNA of the 
      HK-2 cells stimulated with MCP-1 of different concentrations were not 
      significantly different (all P > 0.05). MCP-1 induced expression of a-SMA was 
      only partly inhibited by PD98059 but not by SB203587 or Y27632. MCP-1 
      dose-dependently increased the expression of Snail mRNA of the HK-2 cells 
      compared with those of the negative control cells. The level of Snail mRNA was 
      the highest in the HK-2 cells treated with 100 microg/L MCP-1. CONCLUSION: MCP-1 
      may induce the EMT of renal proximal tubular epithelial cells in vitro, and this 
      effect may involve upregulation of Erk1/2 Map kinase signal pathways and Snail 
      mRNA expression. P38MAPK or Rho kinase signal pathways can not be proven to be 
      involved in MCP-1 induced EMT.
FAU - Li, Hui-Lin
AU  - Li HL
AD  - Division of Nephrology, Peking Union Medical College Hospital, Peking Union 
      Medical Chinese, Chinese Academy of Medical Scieces, Beijing 100730, China.
FAU - Zheng, Fa-Lei
AU  - Zheng FL
FAU - Zhao, Ban
AU  - Zhao B
LA  - chi
PT  - English Abstract
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - China
TA  - Zhonghua Yi Xue Za Zhi
JT  - Zhonghua yi xue za zhi
JID - 7511141
RN  - 0 (Actins)
RN  - 0 (Chemokine CCL2)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Actins/genetics/metabolism
MH  - Blotting, Western
MH  - Cell Line
MH  - Cell Transdifferentiation/*drug effects
MH  - Chemokine CCL2/*pharmacology
MH  - Epithelial Cells/cytology/*drug effects/metabolism
MH  - Fibroblasts/cytology/*drug effects/metabolism
MH  - Humans
MH  - Kidney Tubules/cytology
MH  - Muscle Cells/cytology/drug effects/metabolism
MH  - RNA, Messenger/genetics/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
EDAT- 2008/06/28 09:00
MHDA- 2008/12/23 09:00
CRDT- 2008/06/28 09:00
PHST- 2008/06/28 09:00 [pubmed]
PHST- 2008/12/23 09:00 [medline]
PHST- 2008/06/28 09:00 [entrez]
PST - ppublish
SO  - Zhonghua Yi Xue Za Zhi. 2008 Feb 5;88(6):400-5.