Roles of p38 MAPK and JNK in TGF-β1-induced alveolar epithelial to mesenchymal transition

Abstract

Objective To investigate the roles of p38 MAPK and JNK in transforming growth factor-β1 (TGF-β1)-induced human alveolar epithelial to mesenchymal transition (EMT),and to demonstrate the possible molecular mechanism of idiopathic pulmonary fibrosis.Methods A549 cells were treated with TGF-β1 (3 μg/L) for 48 hours to induce EMT.The expressions of mesenchymal phenotypic markers including desmin,α-smooth muscle actin (α-SMA) and vimentin,and expressions of epithelial phenotypic markers including E cadherin,zonula occludens-1 (ZO-1) and aquaporin-5 (AQP-5) were detected by Western blot.The role of p38 MAPK and JNK in TGF-β1-mediated EMT was investigated using gene silencing and inhibitor SB203580 and SP600125.Results The data showed that TGF-β1 induced A549 cells with alveolar epithelial type Ⅱ cell phenotype to undergo EMT.The process of EMT was accompanied by increased expression of the mesenchymal cell markers α-SMA,desmin and vimentin,and downregulation of the epithelial cell markers E-cadherin,ZO-1 and AQP-5.TGF-β1-induced EMT occurred through phosphorylation of p38 MAPK and JNK and was inhibited by inhibitor SB203580 and SP600125 and gene silencing.Conclusions Our data shows that TGF-β1 induces A549 alveolar epithelial cells to undergo EMT partially via p38 MAPK and JNK activation. Key words: p38 MAPK; c-Jun N-terminal kinase; Alveolar epithelial cells; Epithelial to mesenchymal transition; Transforming growth factor-β1