title: Paraquat induce pulmonary epithelial-mesenchymal transition through transforming growth factor-β1-dependent mechanism.
abstract: Pulmonary fibrosis is prevalent in Paraquat (PQ) poisoning. Transforming growth factor β1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) of Type II alveolar epithelial cells (AT2) contributed to the pulmonary fibrosis in some pulmonary disease. In this study, we investigated whether PQ could induce EMT in AT2 through transforming growth factor β1 (TGF-β1) signal pathway in vitro. Morphological and phenotypic characterizations were evaluated on AT2 cell lines A549 cells in the presence of PQ with or without TGF-β1 inhibitors SB431542 for 5 days. As a result, PQ induced the transition of A549 cells from epithelial morphology to fibroblast-like morphology, associated with the acquisition of migratory properties. Phenotypically, PQ induced-EMT was characterized by loss of epithelial cell markers including E-cadherin and zonula occludens (ZO-1), while up-expressions of mesenchymal cell markers including α-smooth muscle actin (α-SMA) and vimentin, concurrent with increased type I collagen (Col I). SB431542 suppressed PQ-induced EMT via inhibiting expressions of phospho-Smad2 and phospho-Smad3. These findings conclusively demonstrated that the cultured A549 cells underwent EMT in the presence of PQ, and suggested that TGF-β1 played a central role in PQ-induced EMT.
authors.affiliation: Department of Occupational Disease, No.4 West China Hospital of Sichuan University, Chengdu, Sichuan, China.
authors.forename: Linshen
authors.initials: L
authors.lastname: Xie
authors.affiliation: Department of Occupational Disease, No.4 West China Hospital of Sichuan University, Chengdu, Sichuan, China.
authors.forename: Dingzi
authors.initials: D
authors.lastname: Zhou
authors.affiliation: Center for Occupational Respirology, West China School of Public Health, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Xiong
authors.affiliation: Center for Occupational Respirology, West China School of Public Health, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Jia
authors.initials: J
authors.lastname: You
authors.affiliation: Institute of Biomedical Engineering, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: Department of Occupational Disease, No.4 West China Hospital of Sichuan University, Chengdu, Sichuan, China. Electronic address: hxsy_sc@163.com.
authors.forename: Lijun
authors.initials: L
authors.lastname: Peng
mesh_terms: D015153:Blotting, Western; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects* / Q000502:physiology; D005434:Flow Cytometry; D006540:Herbicides / Q000633:toxicity*; D006801:Humans; D008855:Microscopy, Electron, Scanning; D010269:Paraquat / Q000633:toxicity*; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D006540:Herbicides; D053773:Transforming Growth Factor beta1; D010269:Paraquat
keywords: Epithelial–mesenchymal transition; Paraquat; Transforming growth factor β1 (TGF-β1)