ABSTRACT
Idiopathic pulmonary fibrosis (IPF) is characterized by myofibroblast foci in lung parenchyma. Myofibroblasts are thought to originate from epithelial-to-mesenchymal transition (EMT). Wnt1 and lithium chloride (LiCl) induce EMT in alveolar epithelial cells (AECs), but the mechanisms are unclear. AECs were treated with Wnt1 and LiCl, respectively; morphological change and molecular changes of EMT, including E-cadherin, fibronectin, and vimentin, were observed. SB203580 was administrated to test the role of p38 ÐÐÐ Ð signaling in EMT. Then AECs were treated with siRNAs targeting p38 ÐÐÐ Ð to further test the effects of p38 ÐÐÐ Ð, and the role was further confirmed by re-expression of p38 ÐÐÐ Ð. At last P-catenin siRNA was used to test the role of ß-catenin in the EMT process and relationship of ß-catenin and p38 ÐÐÐ Ð was concluded. Exposure of AECs to Wnt1 and LiCl resulted in upregulation of vimentin and fibronectin with subsequent downregulation of E-cadherin. Wnt1 and LiCl stimulated the p38 ÐÐÐ Ð signaling pathways. Perturbing the p38 ÐÐÐ Ð pathway either by SB203580 or through p38 ÐÐÐ Ð siRNA blocked EMT and inhibited fibronetin synthesis, which were reversed by transfection of p38 ÐÐÐ Ð expression plasmid. ß-catenin siRNA attenuated the EMT process and decreased p38 ÐÐÐ Ð phosphorylation, indicating that ß-catenin is involved in the EMTrelated changes through regulation of p38 ÐÐÐ Ð phosphorylation. These findings suggest that p38 ÐÐÐ Ð participates in the pathogenesis of EMT through Wnt pathway and that p38 ÐÐÐ Ð may be a novel target for IPF therapy.