Blocking TGF-β expression inhibits silica particle-induced epithelial-mesenchymal transition in human lung epithelial cells

Environ Toxicol Pharmacol. 2015 Nov;40(3):861-9. doi: 10.1016/j.etap.2015.09.014. Epub 2015 Sep 28.

Abstract

The main characteristic of silicosis is irreversible fibrosis. Certain studies have shown that epithelial-mesenchymal transition (EMT) regulated by transforming growth factor-β (TGF-β) is involved in fibrosis. Thus, we suggest that TGF-β regulated EMT may play an important role in silicosis. In this study, we determined the expression of TGF-β-Smad2/3, EMT- and ECM-related markers in lung epithelial cells treated with silica particle by RT-PCR, western-blot and ELISA. In order to explore the role of TGF-β, we used TGF-β inhibitor in the cell model. We found that the cells lost the expression of epithelial phenotypic markers and acquired increased expression of mesenchymal cells markers with ECM deposition after treatment with silica particle. Moreover, the changes of EMT-related event was restricted in response to TGF-β inhibitor. These findings suggest that EMT is essentially involved in the pathogenesis of fibrosis induced by silica particles and down-regulating the TGF-β expression can inhibit the process of EMT.

Keywords: Epithelial–mesenchymal transition; Extracellular matrix; Silica particle; TGF-β.

MeSH terms

  • Cell Line
  • Cell Proliferation / drug effects
  • Epithelial Cells / cytology
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Epithelial-Mesenchymal Transition / drug effects*
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / metabolism
  • Gene Expression Regulation / drug effects
  • Humans
  • Pyrazoles / pharmacology*
  • Quinolines / pharmacology*
  • Silicon Dioxide / toxicity*
  • Smad2 Protein / genetics
  • Smad2 Protein / metabolism
  • Smad3 Protein / genetics
  • Smad3 Protein / metabolism
  • Transforming Growth Factor beta / genetics*
  • Transforming Growth Factor beta / metabolism

Substances

  • Extracellular Matrix Proteins
  • Pyrazoles
  • Quinolines
  • SMAD2 protein, human
  • SMAD3 protein, human
  • Smad2 Protein
  • Smad3 Protein
  • Transforming Growth Factor beta
  • LY-2157299
  • Silicon Dioxide