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 of EMT in PMC and the latter contributes to subpleural fibrosis.
authors.affiliation: Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Chen
authors.affiliation: Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Key Laboratory of Pulmonary Diseases, Ministry of Health of China, Wuhan, Hubei, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Ye
authors.affiliation: Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Feng-Zhi
authors.initials: FZ
authors.lastname: Li
authors.affiliation: Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Lin-Jie
authors.initials: LJ
authors.lastname: Song
authors.affiliation: Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Mu
authors.affiliation: Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Rao
authors.affiliation: Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Peng-Cheng
authors.initials: PC
authors.lastname: Cai
authors.affiliation: Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Key Laboratory of Pulmonary Diseases, Ministry of Health of China, Wuhan, Hubei, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Xiang
authors.affiliation: Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Key Laboratory of Pulmonary Diseases, Ministry of Health of China, Wuhan, Hubei, China.
authors.forename: Jian-Chu
authors.initials: JC
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology and Toxicology, Medical College of Georgia, Georgia Regents University, Augusta, GA, USA.
authors.forename: Yunchao
authors.initials: Y
authors.lastname: Su
authors.affiliation: Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Key Laboratory of Pulmonary Diseases, Ministry of Health of China, Wuhan, Hubei, China. Electronic address: 814643835@qq.com.
authors.forename: Jian-Bao
authors.initials: JB
authors.lastname: Xin
authors.affiliation: Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Key Laboratory of Pulmonary Diseases, Ministry of Health of China, Wuhan, Hubei, China. Electronic address: whmawl@aliyun.com.
authors.forename: Wan-Li
authors.initials: WL
authors.lastname: Ma
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D001761:Bleomycin / Q000633:toxicity*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D004848:Epithelium / Q000187:drug effects / Q000473:pathology; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000473:pathology
chemical_list: D000903:Antibiotics, Antineoplastic; D001761:Bleomycin
keywords: Bleomycin; Collagen; Epithelial–mesenchymal transition (EMT); Fibrosis; Lung; Pleural mesothelial cell