Involvement of epithelial-to-mesenchymal transition and associated transforming growth factor-β/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 α‑smooth‑muscle actin and vimentin was significantly increased in rat lung tissues and A549 cells following PQ treatment. Transforming growth factor (TGF)‑β/Smad signaling was also induced by PQ as evidenced by increased expression of TGF‑β1 and Smad2. However, PQ‑induced EMT in A549 cells was abolished by transfection with TGF‑β1‑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-β/Smad signaling was involved in PQ-induced EMT.
Department of Nephrology, Tianjin First Center Hospital, Tianjin 300192, P.R. China.
Ying-Ying
YY
Han
Department of Emergency Medicine, Tianjin First Center Hospital, Tianjin 300192, P.R. China.
Peng
P
Shen
Department of Nephrology, Tianjin First Center Hospital, Tianjin 300192, P.R. China.
Wen-Xiu
WX
Chang
D000199:Actins / Q000378:metabolism; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000502:physiology*; D006540:Herbicides / Q000633:toxicity; D006801:Humans; D008297:Male; D010269:Paraquat / Q000633:toxicity; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D051899:Smad2 Protein / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014746:Vimentin / Q000378:metabolism
D000199:Actins; D015820:Cadherins; D006540:Herbicides; D010269:Paraquat; D034741:RNA, Small Interfering; D051899:Smad2 Protein; D053773:Transforming Growth Factor beta1; D014746:Vimentin; C498862:Acta2 protein, rat