Bleomycin induced epithelial-mesenchymal transition (EMT) in pleural mesothelial cells

Li Jun Chen, Hong Ye, Qian Zhang, Feng Zhi Li, Lin Jie Song, Jie Yang, Qing Mu, Shan Shan Rao, Peng Cheng Cai, Fei Xiang, Jian Chu Zhang, Yunchao Su, Jian Bao Xin, Wan Li Ma

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease characterized by the development of subpleural foci of myofibroblasts that contribute to the exuberant fibrosis. Recent studies revealed that pleural mesothelial cells (PMCs) undergo epithelial-mesenchymal transition (EMT) and play a pivotal role in IPF. In animal model, bleomycin induces pulmonary fibrosis exhibiting subpleural fibrosis similar to what is seen in human IPF. It is not known yet whether bleomycin induces EMT in PMCs. In the present study, PMCs were cultured and treated with bleomycin. The protein levels of collagen-I, mesenchymal phenotypic markers (vimentin and α-smooth muscle actin), and epithelial phenotypic markers (cytokeratin-8 and E-cadherin) were measured by Western blot. PMC migration was evaluated using wound-healing assay of culture PMCs in vitro, and in vivo by monitoring the localization of PMC marker, calretinin, in the lung sections of bleomycin-induced lung fibrosis. The results showed that bleomycin induced increases in collagen-I synthesis in PMC. Bleomycin induced significant increases in mesenchymal phenotypic markers and decreases in epithelial phenotypic markers in PMC, and promoted PMC migration in vitro and in vivo. Moreover, TGF-β1-Smad2/3 signaling pathway involved in the EMT of PMC was demonstrated. Taken together, our results indicate that bleomycin induces characteristic changes of EMT in PMC and the latter contributes to subpleural fibrosis.

Original languageEnglish (US)
Pages (from-to)75-82
Number of pages8
JournalToxicology and Applied Pharmacology
Volume283
Issue number2
DOIs
StatePublished - Mar 1 2015

Keywords

  • Bleomycin
  • Collagen
  • Epithelial-mesenchymal transition (EMT)
  • Fibrosis
  • Lung
  • Pleural mesothelial cell

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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  • Cite this

    Chen, L. J., Ye, H., Zhang, Q., Li, F. Z., Song, L. J., Yang, J., Mu, Q., Rao, S. S., Cai, P. C., Xiang, F., Zhang, J. C., Su, Y., Xin, J. B., & Ma, W. L. (2015). Bleomycin induced epithelial-mesenchymal transition (EMT) in pleural mesothelial cells. Toxicology and Applied Pharmacology, 283(2), 75-82. https://doi.org/10.1016/j.taap.2015.01.004