title: Smad7 inhibits TGF-β1-induced MCP-1 upregulation through a MAPK/p38 pathway in rat peritoneal mesothelial cells.
abstract: OBJECTIVE
  The TGF-β1/Smad signaling pathway is subject to inhibition by Smad7. High expression of Smad7 in the peritoneum of rats can delay and attenuate not only peritoneal fibrosis, but also monocyte infiltration into the peritoneum. The aim of this study was to investigate the anti-inflammatory mechanism of Smad7 in peritoneal fibrosis.
  
  
  METHODS
  Rat peritoneal mesothelial cells were stimulated with TGF-β1, and the expression of MCP-1 protein and mRNA was measured. Furthermore, the expression of MCP-1 was determined following inhibition of TGF-β/Smad or p38 signaling using Smad7 transfection or SB203580 (10 μmol/L), respectively. The effect of exogenous Smad7 and SB203580 on activation of the TGF-β/Smad and p38 signaling pathways was also studied.
  
  
  RESULTS
  TGF-β1 significantly upregulated the expression of MCP-1 at both the protein and mRNA level in a time-dependent manner. Exogenous Smad7 and SB203580 markedly inhibited TGF-β1-induced MCP-1 expression. Moreover, high expression of exogenous Smad7 not only inhibited phosphorylation of Smad2 and Smad3, but also diminished the level of phosphorylated p38. However, SB203580 had no effect on the phosphorylation of Smad2 and Smad3.
  
  
  CONCLUSIONS
  TGF-β1 exhibits pro-inflammatory effects through the upregulation of MCP-1 in peritoneal fibrosis. Smad7 inhibits TGF-β1 induced MCP-1 upregulation through a MAPK/p38-dependent pathway.
authors.affiliation: Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Li
authors.forename: Ling
authors.initials: L
authors.lastname: Ye
authors.forename: Weiying
authors.initials: W
authors.lastname: Chen
authors.forename: Xueqing
authors.initials: X
authors.lastname: Yu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics*; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D066298:In Vitro Techniques; D008297:Male; D010446:Peptide Fragments / Q000096:biosynthesis / Q000235:genetics*; D056627:Peritoneal Fibrosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010537:Peritoneum / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D051906:Smad7 Protein / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D018932:Chemokine CCL2; D010446:Peptide Fragments; D012333:RNA, Messenger; D051906:Smad7 Protein; D053773:Transforming Growth Factor beta1; C508645:monocyte chemoattractant protein 1 (66-77)