title: HIF-1α regulates EMT via the Snail and β-catenin pathways in paraquat poisoning-induced early pulmonary fibrosis.
abstract: Paraquat (PQ) poisoning-induced pulmonary fibrosis is one of the primary causes of death in patients with PQ poisoning. Hypoxia-inducible factor-1α (HIF-1α) and epithelial-mesenchymal transition (EMT) are involved in the progression of pulmonary fibrosis. Snail and β-catenin are two other factors involved in promoting EMT. However, the relationship among HIF-1α, Snail and β-catenin in PQ poisoning-induced pulmonary fibrosis is not clear. Our research aimed to determine whether the regulation of HIF-1α in EMT occurs via the Snail and β-catenin pathways in PQ poisoning-induced pulmonary fibrosis. Sixty-six Sprague-Dawley rats were randomly and evenly divided into a control group and a PQ group. The PQ group was treated with an intragastric infusion of a 20% PQ solution (50 mg/kg) for 2, 6, 12, 24, 48 and 72 hrs. A549 and RLE-6TN cell lines were transfected with HIF-1α siRNA for 48 hrs before being exposed to PQ. Western blotting, real-time quantitative PCR, immunofluorescence, immunohistochemistry and other assays were used in our research. In vivo, the protein levels of HIF-1α and α-SMA were increased at 2 hrs and the level of ZO-1 (Zonula Occluden-1) was reduced at 12 hrs. In vitro, the transient transfection of HIF-1α siRNA resulted in a decrease in the degree of EMT. The expression levels of Snail and β-catenin were significantly reduced when HIF-α was silenced. These data demonstrate that EMT may be involved in PQ poisoning-induced pulmonary fibrosis and regulated by HIF-1α via the Snail and β-catenin pathways. Hypoxia-inducible factor-1α may be a therapeutic target for the treatment of PQ poisoning-induced pulmonary fibrosis.
authors.affiliation: Department of Critical Care Medicine, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Critical Care Medicine, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Jiuting
authors.initials: J
authors.lastname: Tan
authors.affiliation: Department of Critical Care Medicine, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Xie
authors.affiliation: Department of Critical Care Medicine, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Critical Care Medicine, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Meng
authors.affiliation: Department of Critical Care Medicine, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Ruilan
authors.initials: R
authors.lastname: Wang
mesh_terms: D000072283:A549 Cells; D000818:Animals; D002460:Cell Line; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D008297:Male; D010269:Paraquat; D011650:Pulmonary Alveoli / Q000378:metabolism / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors / Q000235:genetics* / Q000378:metabolism; D062826:Zonula Occludens-1 Protein / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism
chemical_list: C495268:Ctnnb1 protein, rat; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D034741:RNA, Small Interfering; D000071250:Snail Family Transcription Factors; C569044:Tjp1 protein, rat; D062826:Zonula Occludens-1 Protein; D051176:beta Catenin; C000604452:snai1 protein, rat; D010269:Paraquat
keywords: epithelial-mesenchymal transition; hypoxia-inducible factor-1α; paraquat; pulmonary fibrosis