title: MAPK pathway mediates epithelial-mesenchymal transition induced by paraquat in alveolar epithelial cells.
abstract: Epithelial-mesenchymal transition (EMT) is believed to be involved in lung fibrosis process induced by paraquat (PQ); however, the molecular mechanism of this process has not been clearly established. The present study investigated the potential involvement of EMT after PQ poisoning. The expressions of EMT markers, such as E-cadherin and α-smooth muscle actin (α-SMA), at multiple time points after exposure to different concentrations of PQ were evaluated by western blot analysis. Following PQ treatment, EMT induction was observed under microscopy. Related fibrosis genes, including Matrix metalloproteinase 2 (MMP-2), Matrix metalloproteinase 9 (MMP-9), collagens type I (COL I), and type III (COL III), were also evaluated by measuring their mRNA levels using RT-PCR analysis. Signaling pathways were analyzed using selective pharmacological inhibitors for MAPK. Cell migration ability was evaluated by scratch wound and Transwell assays. The data showed that PQ-induced epithelial RLE-6NT cells to develop mesenchymal cell characteristics, as indicated by a significant decrease in the epithelial marker E-cadherin and a significant increase in the extracellular matrix (ECM) marker α-smooth muscle actin in a dose and time-dependent manner. Moreover, PQ-treated RLE-6NT cells had an EMT-like phenotype with elevated expression of MMP-2, MMP-9, and COL I and COL III and enhanced migration ability. Signal pathway analysis revealed that PQ-induced EMT led to ERK-1 and Smad2 phosphorylation through activation of the MAPK pathway. The results of the current study indicate that PQ-induced pulmonary fibrosis occurs via EMT, which is mediated by the MAPK pathway. This implies that the MAPK pathway is a promising therapeutic target in alveolar epithelial cells. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1407-1414, 2016.
authors: The Department of Occupational and Environmental Health, School of Public Health, Ningxia Medical University, 1160 Shengli Street, Xingqing District, Yinchuan, 750004, People's Republic of China.
authors: Min
authors: M
authors: Huang
authors: The Department of Occupational and Environmental Health, School of Public Health, Ningxia Medical University, 1160 Shengli Street, Xingqing District, Yinchuan, 750004, People's Republic of China.
authors: Ya-Peng
authors: YP
authors: Wang
authors: The Department of Occupational and Environmental Health, School of Public Health, Ningxia Medical University, 1160 Shengli Street, Xingqing District, Yinchuan, 750004, People's Republic of China.
authors: Ling-Qin
authors: LQ
authors: Zhu
authors: The Department of Occupational and Environmental Health, School of Public Health, Ningxia Medical University, 1160 Shengli Street, Xingqing District, Yinchuan, 750004, People's Republic of China.
authors: Qian
authors: Q
authors: Cai
authors: The Department of Occupational and Environmental Health, School of Public Health, Ningxia Medical University, 1160 Shengli Street, Xingqing District, Yinchuan, 750004, People's Republic of China.
authors: Hong-Hui
authors: HH
authors: Li
authors: The Department of Occupational and Environmental Health, School of Public Health, Ningxia Medical University, 1160 Shengli Street, Xingqing District, Yinchuan, 750004, People's Republic of China. professorhfyang@outlook.com.
authors: Hui-Fang
authors: HF
authors: Yang
mesh_terms: D056809:Alveolar Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D010269:Paraquat / Q000633:toxicity*; D010766:Phosphorylation / Q000187:drug effects; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D051899:Smad2 Protein / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D015820:Cadherins; D051899:Smad2 Protein; D053773:Transforming Growth Factor beta1; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D010269:Paraquat
keywords: MAPK; epithelial-mesenchymal transition; lung fibrosis; paraquat