Ying-Hua Ying1, Xiao-Ping Lin2, Hong-bin Zhou1, Yin-fang Wu1, Fu-gui Yan1, Wen Hua1, Li-Xia Xia1, Zhang-wei Qiu1, Zhi-Hua Chen1, Wen Li3, Hua-Hao Shen4. 1. Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China. 2. Department of Respiratory and Critical Care Medicine, Second Hospital of Fujian Medical University, Quanzhou, Fujian 362000, China. 3. Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China. Electronic address: liwenzjhz0408@163.com. 4. 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.
Abstract
BACKGROUND AND 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. CONCLUSION: Nrf2 negatively regulated smoking-induced mucus production in vitro and in vivo, suggesting therapeutic potentials of this factor in airway diseases with hypersecreted mucus.
BACKGROUND AND 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. CONCLUSION:Nrf2 negatively regulated smoking-induced mucus production in vitro and in vivo, suggesting therapeutic potentials of this factor in airway diseases with hypersecreted mucus.