title: Nuclear erythroid 2 p45-related factor-2 Nrf2 ameliorates cigarette smoking-induced mucus overproduction in airway epithelium and mouse lungs.
abstract: OBJECTIVE
  Nuclear erythroid 2 p45-related factor-2 (Nrf2) is known to play important roles in airway disorders, whereas little has been investigated about its direct role in airway mucus hypersecretion. The aim of this study is to determine whether this factor could protect pulmonary epithelium and mouse airway from cigarette-induced mucus overproduction.
  
  
  METHODS
  Using genetic approaches, the role of Nrf2 on cigarette smoking extracts (CSE) induced MUC5AC expression was investigated in lung A549 cells. Nrf2 deficiency mice were smoked for various periods, and the airway inflammation and mucus production was characterized.
  
  
  RESULTS
  Acute smoking exposure induced expression of MUC5AC and Nrf2 in both A549 cells and mouse lungs. Genetic ablation of Nrf2 augmented, whereas overexpression of this molecule ameliorated CSE-induced expression of MUC5AC. Nrf2 knockout mice, after exposure to cigarette smoking, displayed enhanced airway inflammation and mucus production.
  
  
  CONCLUSIONS
  Nrf2 negatively regulated smoking-induced mucus production in vitro and in vivo, suggesting therapeutic potentials of this factor in airway diseases with hypersecreted mucus.
authors.affiliation: Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China.
authors.forename: Ying-Hua
authors.initials: YH
authors.lastname: Ying
authors.affiliation: Department of Respiratory and Critical Care Medicine, Second Hospital of Fujian Medical University, Quanzhou, Fujian 362000, China.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Lin
authors.affiliation: Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China.
authors.forename: Hong-bin
authors.initials: HB
authors.lastname: Zhou
authors.affiliation: Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China.
authors.forename: Yin-fang
authors.initials: YF
authors.lastname: Wu
authors.affiliation: Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China.
authors.forename: Fu-gui
authors.initials: FG
authors.lastname: Yan
authors.affiliation: Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Hua
authors.affiliation: Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China.
authors.forename: Li-Xia
authors.initials: LX
authors.lastname: Xia
authors.affiliation: Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China.
authors.forename: Zhang-wei
authors.initials: ZW
authors.lastname: Qiu
authors.affiliation: Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China.
authors.forename: Zhi-Hua
authors.initials: ZH
authors.lastname: Chen
authors.affiliation: Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China. Electronic address: liwenzjhz0408@163.com.
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China; State Key Laboratory of Respiratory Diseases, Guangzhou 510120, China. Electronic address: huahaoshen@163.com.
authors.forename: Hua-Hao
authors.initials: HH
authors.lastname: Shen
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000378:metabolism; D008168:Lung / Q000503:physiopathology*; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D055271:Mucin 5AC / Q000235:genetics / Q000378:metabolism; D009093:Mucus / Q000187:drug effects* / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D020545:Respiratory Mucosa / Q000503:physiopathology*; D012907:Smoking / Q000009:adverse effects*
chemical_list: C524678:MUC5AC protein, human; D055271:Mucin 5AC; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; C495636:Nfe2l2 protein, mouse; D017382:Reactive Oxygen Species
keywords: Cigarette smoking; MUC5AC; Mucus production; Nrf2