title: Lysyl oxidase promotes epithelial-to-mesenchymal transition during paraquat-induced pulmonary fibrosis.
abstract: Lysyl oxidase (LOX) is a copper-dependent amine oxidase that plays a critical role in pulmonary fibrosis. Our previous study demonstrated that epithelial-to-mesenchymal transition (EMT) was strongly associated with paraquat (PQ) induced pulmonary fibrosis. This present study was aimed to evaluate the potential involvement of LOX on EMT in the process of pulmonary fibrosis induced by PQ. We established an in vivo rat model and an in vitro cell model induced by PQ treatment and found that LOX protein expression was significantly up-regulated and collagen deposition was enhanced in rats. The EMT process was strongly found in A549 and RLE-6TN cells after PQ exposure. After inactivating LOX with an inhibitor, pulmonary fibrosis was significantly reduced and EMT was also suppressed. Additionally, small interfering RNA (siRNA) targeting LOX was used to silence LOX expression to observe EMT in A549 cells. As a result, LOX could promote the progress of EMT, and inactivating LOX alleviated the EMT process in PQ-induced pulmonary fibrosis and mesenchymal-to-epithelial transition (MET) occurred after inactivating LOX in vitro and in vivo. In conclusion, LOX could promote the progress of EMT and inactivating LOX alleviated EMT in PQ-induced pulmonary fibrosis. Therefore, LOX could potentially be a new candidate therapeutic target for pulmonary fibrosis induced by PQ by regulating the balance between EMT and MET.
authors.affiliation: Department of Intensive Care Unit, Shanghai General Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 201620, China. wangyusun@hotmail.com.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Intensive Care Unit, Shanghai General Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 201620, China. wangyusun@hotmail.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Intensive Care Unit, Shanghai General Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 201620, China. wangyusun@hotmail.com.
authors.forename: Jiuting
authors.initials: J
authors.lastname: Tan
authors.affiliation: Department of Intensive Care Unit, Shanghai General Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 201620, China. wangyusun@hotmail.com.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Meng
authors.affiliation: Department of Intensive Care Unit, Shanghai General Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 201620, China. wangyusun@hotmail.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Xie
authors.affiliation: Department of Intensive Care Unit, Shanghai General Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 201620, China. wangyusun@hotmail.com.
authors.forename: Ruilan
authors.initials: R
authors.lastname: Wang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D008297:Male; D010269:Paraquat; D008249:Protein-Lysine 6-Oxidase / Q000502:physiology*; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D017207:Rats, Sprague-Dawley
chemical_list: D008249:Protein-Lysine 6-Oxidase; D010269:Paraquat