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

• Published in: Toxicology and applied pharmacology 2015-03, Vol.283 (2), p.75-82
• Main Authors: Chen, Li-Jun, Ye, Hong, Zhang, Qian, Li, Feng-Zhi, Song, Lin-Jie, Yang, Jie, Mu, Qing, Rao, Shan-Shan, Cai, Peng-Cheng, Xiang, Fei, Zhang, Jian-Chu, Su, Yunchao, Xin, Jian-Bao, Ma, Wan-Li
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; ACTIN; ANIMALS; Antibiotics, Antineoplastic - toxicity; BLEOMYCIN; Bleomycin - toxicity; Cell Line; COLLAGEN; Dose-Response Relationship, Drug; Epithelial-Mesenchymal Transition - drug effects; Epithelial–mesenchymal transition (EMT); Epithelium - drug effects; Epithelium - pathology; FIBROSIS; HEALING; HUMAN POPULATIONS; Humans; IN VITRO; IN VIVO; Lung; Lung - drug effects; Lung - pathology; LUNGS; Male; Mice; Mice, Inbred C57BL; MONITORING; MUSCLES; Pleural mesothelial cell; Respiratory Mucosa - drug effects; Respiratory Mucosa - pathology; SIGNALS; SYNTHESIS; WOUNDS
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/j.taap.2015.01.004

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. •Bleomycin induces collagen-I synthesis in pleural mesothelial cells (PMCs).•Bleomycin induces increases in vimentin and α-SMA protein in PMCs.•Bleomycin induces decreases in cytokeratin-8 and E-cadherin protein in PMCs•TGF-β1-Smad2/3 signaling pathway is involved in the PMC EMT induced by bleomycin