Involvement of epithelial-to-mesenchymal transition and associated transforming growth factor-/Smad signaling in paraquat-induced pulmonary fibrosis

Paraquat (PQ) is a highly toxic herbicide which is able to induce pulmonary fibrosis in humans and animals. The epithelial-to-mesenchymal transition (EMT) was demonstrated to be an important factor in pulmonary fibrosis. However, it has remained elusive whether PQ induces pulmonary fibrosis via EMT, which was therefore investigated in the present study. In addition, the underlying mechanisms of PQ-induced EMT were examined in vitro. Hematoxylin and eosin staining of rat lung tissues demonstrated that PQ induced pulmonary fibrosis in vivo. Western blot analysis then revealed that the expression of epithelial cell marker E-cadherin was significantly decreased, while the expression of mesenchymal markers -smooth-muscle actin and vimentin was significantly increased in rat lung tissues and A549 cells following PQ treatment. Transforming growth factor (TGF)-/Smad signaling was also induced by PQ as evidenced by increased expression of TGF-1 and Smad2. However, PQ-induced EMT in A549 cells was abolished by transfection with TGF-1-specific small hairpin RNA. In conclusion, the present study demonstrated that PQ induced EMT in vivo and in vitro, which may be an important process in the development of PQ-induced pulmonary fibrosis. In addition, TGF-/Smad signaling was involved in PQ-induced EMT.