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

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 ofmore » EMT in PMC and the latter contributes to subpleural fibrosis. - Highlights: • 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.« less

Authors:
 [1];  [2];  [3]; ; ; ; ;  [1];  [2];  [4]; ;  [1];  [3];  [5];  [1];  [3];  [1];  [3]
  1. Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei (China)
  2. Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei (China)
  3. (China)
  4. Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei (China)
  5. Department of Pharmacology and Toxicology, Medical College of Georgia, Georgia Regents University, Augusta, GA (United States)
Publication Date:
OSTI Identifier:
22465702
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 283; Journal Issue: 2; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ACTIN; ANIMALS; BLEOMYCIN; COLLAGEN; FIBROSIS; HEALING; HUMAN POPULATIONS; IN VITRO; IN VIVO; LUNGS; MONITORING; MUSCLES; SIGNALS; SYNTHESIS; WOUNDS

Citation Formats

Chen, Li-Jun, Ye, Hong, Key Laboratory of Pulmonary Diseases, Ministry of Health of China, Wuhan, Hubei, Zhang, Qian, Li, Feng-Zhi, Song, Lin-Jie, Yang, Jie, Mu, Qing, Rao, Shan-Shan, Cai, Peng-Cheng, Xiang, Fei, Zhang, Jian-Chu, Key Laboratory of Pulmonary Diseases, Ministry of Health of China, Wuhan, Hubei, Su, Yunchao, Xin, Jian-Bao, E-mail: 814643835@qq.com, Key Laboratory of Pulmonary Diseases, Ministry of Health of China, Wuhan, Hubei, Ma, Wan-Li, E-mail: whmawl@aliyun.com, and Key Laboratory of Pulmonary Diseases, Ministry of Health of China, Wuhan, Hubei. Bleomycin induced epithelial–mesenchymal transition (EMT) in pleural mesothelial cells. United States: N. p., 2015. Web. doi:10.1016/J.TAAP.2015.01.004.
Chen, Li-Jun, Ye, Hong, Key Laboratory of Pulmonary Diseases, Ministry of Health of China, Wuhan, Hubei, Zhang, Qian, Li, Feng-Zhi, Song, Lin-Jie, Yang, Jie, Mu, Qing, Rao, Shan-Shan, Cai, Peng-Cheng, Xiang, Fei, Zhang, Jian-Chu, Key Laboratory of Pulmonary Diseases, Ministry of Health of China, Wuhan, Hubei, Su, Yunchao, Xin, Jian-Bao, E-mail: 814643835@qq.com, Key Laboratory of Pulmonary Diseases, Ministry of Health of China, Wuhan, Hubei, Ma, Wan-Li, E-mail: whmawl@aliyun.com, & Key Laboratory of Pulmonary Diseases, Ministry of Health of China, Wuhan, Hubei. Bleomycin induced epithelial–mesenchymal transition (EMT) in pleural mesothelial cells. United States. doi:10.1016/J.TAAP.2015.01.004.
Chen, Li-Jun, Ye, Hong, Key Laboratory of Pulmonary Diseases, Ministry of Health of China, Wuhan, Hubei, Zhang, Qian, Li, Feng-Zhi, Song, Lin-Jie, Yang, Jie, Mu, Qing, Rao, Shan-Shan, Cai, Peng-Cheng, Xiang, Fei, Zhang, Jian-Chu, Key Laboratory of Pulmonary Diseases, Ministry of Health of China, Wuhan, Hubei, Su, Yunchao, Xin, Jian-Bao, E-mail: 814643835@qq.com, Key Laboratory of Pulmonary Diseases, Ministry of Health of China, Wuhan, Hubei, Ma, Wan-Li, E-mail: whmawl@aliyun.com, and Key Laboratory of Pulmonary Diseases, Ministry of Health of China, Wuhan, Hubei. Sun . "Bleomycin induced epithelial–mesenchymal transition (EMT) in pleural mesothelial cells". United States. doi:10.1016/J.TAAP.2015.01.004.
@article{osti_22465702,
title = {Bleomycin induced epithelial–mesenchymal transition (EMT) in pleural mesothelial cells},
author = {Chen, Li-Jun and Ye, Hong and Key Laboratory of Pulmonary Diseases, Ministry of Health of China, Wuhan, Hubei and Zhang, Qian and Li, Feng-Zhi and Song, Lin-Jie and Yang, Jie and Mu, Qing and Rao, Shan-Shan and Cai, Peng-Cheng and Xiang, Fei and Zhang, Jian-Chu and Key Laboratory of Pulmonary Diseases, Ministry of Health of China, Wuhan, Hubei and Su, Yunchao and Xin, Jian-Bao, E-mail: 814643835@qq.com and Key Laboratory of Pulmonary Diseases, Ministry of Health of China, Wuhan, Hubei and Ma, Wan-Li, E-mail: whmawl@aliyun.com and Key Laboratory of Pulmonary Diseases, Ministry of Health of China, Wuhan, Hubei},
abstractNote = {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. - Highlights: • 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.},
doi = {10.1016/J.TAAP.2015.01.004},
journal = {Toxicology and Applied Pharmacology},
number = 2,
volume = 283,
place = {United States},
year = {Sun Mar 01 00:00:00 EST 2015},
month = {Sun Mar 01 00:00:00 EST 2015}
}