PMID- 16321320
OWN - NLM
STAT- MEDLINE
DCOM- 20130624
LR  - 20051202
IS  - 0376-2491 (Print)
IS  - 0376-2491 (Linking)
VI  - 85
IP  - 37
DP  - 2005 Sep 28
TI  - [Effect of bone morphogenetic protein-7 on monocyte chemoattractant protein-1 
      induced epithelial-myofibroblast transition and TGF-beta1-Smad 3 signaling 
      pathway of HKC cells].
PG  - 2607-12
AB  - OBJECTIVE: To examine the effect of Bone Morphogenetic protein-7 (BMP-7) on 
      Monocyte chemoattractant protein-1 (MCP-1) induced epithelial-myofibroblast 
      transition (EMT) in cultured renal proximal tubular cells (HK-2) and the 
      relationship between TGF-beta1-smad 3 expressions and MCP-1 induced EMT. METHODS: 
      The cultured HK-2 cells were divided into six groups: a, negative control, b, 
      treated with TGF-beta1 (5 ng/ml) as positive control, c, treated with MCP-1 (0.1, 
      1, 10, 50 ng/ml), d, treated with BMP-7 (0.1, 1, 10, 50 ng/ml), e. co-treated 
      with MCP-1 (1 ng/ml) and MCP-1 neutralized antibody (1 ng/ml), f. co-treated with 
      MCP-1 (1 ng/ml) and BMP-7 (50 ng/ml). alpha-Smooth Muscle Actin (alpha-SMA) mRNA 
      expression of HK-2 cells was assessed with RT-PCR. Secretion of type I collagen 
      was assessed with RT-PCR and ELISA, respectively. TGF-beta1 and Smad 3 
      expressions were assessed with Western blot. RESULTS: alpha-SMA mRNA expression 
      significantly increased in HK-2 cells treated with MCP-1 (0.1, 1 ng/ml) compared 
      with negative controls (5.97 +/- 0.35, 23.36 +/- 1.37 vs. 0.59 +/- 0.38, P < 
      0.01). alpha-SMA mRNA expression of HK-2 cells concomitantly treated with MCP-1 
      neutralized antibody or BMP-7 (50 ng/ml) and MCP-1 (1 ng/ml) significantly 
      decreased than that in cells treated with MCP-1 (1 ng/ml) alone (1.93 +/- 0.34, 
      13.59 +/- 0.38 vs. 36.36 +/- 1.37, P < 0.01). Secretion of type I collagen of the 
      cells treated with MCP-1 (0.1, 1 ng/ml) markedly increased compared with negative 
      control (1751 +/- 34, 1876 +/- 45 vs. 1450 +/- 62; P < 0.01). The secretion of 
      type I collagen of the supernatant were also significantly lower than that in 
      cells treated with MCP-1 (1 ng/ml) alone (1462 +/- 56, 1596 +/- 34 vs. 1876 +/- 
      45, P < 0.05). The expression of TGF-beta1 and Smad 3 of HK-2 cells treated with 
      MCP-1 (1 ng/ml) were markedly higher than that of negative controls, respectively 
      (36.31 +/- 1.37 vs. 0.75 +/- 0.16, P < 0.01; 56.98 +/- 2.61 vs. 23.05 +/- 1.82, P 
      < 0.01). The expressions of TGF-beta1 and Smad 3 in HK-2 cells treated 
      concomitantly with MCP-1 neutralized antibody or BMP-7 (50 ng/ml) and MCP-1 (1 
      ng/ml) were markedly decreased than that treated with MCP-1 alone, respectively. 
      (4.61 +/- 0.74, 23.74 +/- 2.14 vs. 36.31 +/- 1.37, P < 0.01; 19.63 +/- 1.65, 
      37.06 +/- 1.82 vs. 56.98 +/- 2.61, P < 0.01). The expressions of TGF-beta1 and 
      Smad 3 in HK-2 cells treated concomitantly with MCP-1 neutralized antibody or 
      BMP-7 (50 ng/ml) and MCP-1 (1 ng/ml) were markedly decreased than that treated 
      with MCP-1 alone, respectively. (4.61 +/- 0.74, 23.74 +/- 2.14 vs. 36.31 +/- 
      1.37, P < 0.01; 19.63 +/- 1.65, 37.06 +/- 1.82 vs. 56.98 +/- 2.61, P < 0.01). 
      CONCLUSIONS: The results documented that MCP-1 may induce EMT of HK-2 cells in 
      vitro, and this effect is related to up-regulated expression of TGF-beta1 and 
      Smad 3. BMP-7 may partially inhibit MCP-1-induced EMT and this effect is related 
      to the downregulated expression of TGF-beta1 and Smad 3 of the cells. The results 
      also suggest that MCP-1 induced EMT may involve the TGF-beta1-independent pathway 
      of the cells.
FAU - Tan, Xiao-yue
AU  - Tan XY
AD  - Division of Nephrology, Peking Union Medical College Hospital, PUMC & CAMS, 
      Beijing 100730, China.
FAU - Zheng, Fa-lei
AU  - Zheng FL
FAU - Zhou, Qiu-gen
AU  - Zhou QG
FAU - Duan, Lin
AU  - Duan L
FAU - Li, Yan
AU  - Li Y
LA  - chi
PT  - English Abstract
PT  - Journal Article
PL  - China
TA  - Zhonghua Yi Xue Za Zhi
JT  - Zhonghua yi xue za zhi
JID - 7511141
RN  - 0 (Actins)
RN  - 0 (Bone Morphogenetic Protein 7)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Smad3 Protein)
RN  - 0 (Transforming Growth Factor beta1)
SB  - IM
MH  - Actins/metabolism
MH  - Bone Morphogenetic Protein 7/*pharmacology
MH  - Cell Differentiation/drug effects
MH  - Cell Line
MH  - Chemokine CCL2/*pharmacology
MH  - Epithelial Cells/cytology/metabolism
MH  - *Epithelial-Mesenchymal Transition
MH  - Humans
MH  - Kidney Tubules, Proximal/cytology
MH  - Signal Transduction/drug effects
MH  - Smad3 Protein/*metabolism
MH  - Transforming Growth Factor beta1/*metabolism
EDAT- 2005/12/03 09:00
MHDA- 2013/06/26 06:00
CRDT- 2005/12/03 09:00
PHST- 2005/12/03 09:00 [pubmed]
PHST- 2013/06/26 06:00 [medline]
PHST- 2005/12/03 09:00 [entrez]
PST - ppublish
SO  - Zhonghua Yi Xue Za Zhi. 2005 Sep 28;85(37):2607-12.