MAPK pathway mediates epithelial‐mesenchymal transition induced by paraquat in alveolar epithelial cells

• DOI: 10.1002/tox.22146
• Publication Date: 2015-04-15T05:24:07Z
• Authors: Min Huang; Ya‐Peng Wang; Ling‐Qin Zhu; Qian Cai; Hong‐Hui Li; Hui‐Fang Yang
• Keywords: Paraquat; 0303 health sciences; Epithelial-Mesenchymal Transition; MAP Kinase Signaling System; Pulmonary Fibrosis; Smad2 Protein; Cadherins; 3. Good health; Rats; Transforming Growth Factor beta1; 03 medical and health sciences; Matrix Metalloproteinase 9; Cell Movement; Alveolar Epithelial Cells; Animals; Matrix Metalloproteinase 2; Phosphorylation; Cells, Cultured

ABSTRACT Epithelial‐mesenchymal transition (EMT) is believed to be involved in lung fibrosis process induced by paraquat (PQ); however, the molecular mechanism of this has not been clearly established. The present study investigated potential involvement EMT after PQ poisoning. expressions markers, such as E‐cadherin and α‐smooth muscle actin (α‐SMA), at multiple time points exposure different concentrations were evaluated western blot analysis. Following treatment, induction was observed under microscopy. Related genes, including Matrix metalloproteinase 2 (MMP‐2), 9 (MMP‐9), collagens type I (COL I), III III), also measuring their mRNA levels using RT‐PCR Signaling pathways analyzed selective pharmacological inhibitors for MAPK. Cell migration ability scratch wound Transwell assays. data showed that PQ‐induced epithelial RLE‐6NT cells develop mesenchymal cell characteristics, indicated a significant decrease marker increase extracellular matrix (ECM) dose time‐dependent manner. Moreover, PQ‐treated had an EMT‐like phenotype with elevated expression MMP‐2, MMP‐9, COL enhanced ability. Signal pathway analysis revealed led ERK‐1 Smad2 phosphorylation through activation MAPK pathway. results current indicate pulmonary occurs via EMT, which mediated This implies promising therapeutic target alveolar cells. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1407–1414, 2016.