Ubiquitin-specific protease-7 promotes expression of airway mucin MUC5AC via the NF-κB signaling pathway
Yi-Jing He,
Yi-Rong Chen,
Jia-Rui Song,
Jin-Xiu Jiang,
Ting-Ting Liu,
Jia-Yao Li,
Li Liu,
Jing Jia
Affiliations
Yi-Jing He
Department of Anesthesiology, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan Province, China; Laboratory of Neurological Diseases and Brain Function, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan Province, China
Yi-Rong Chen
Department of Anesthesiology, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan Province, China; Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan Province, China
Jia-Rui Song
Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan Province, China
Jin-Xiu Jiang
Department of Anesthesiology, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan Province, China; Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan Province, China
Ting-Ting Liu
Department of Anesthesiology, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan Province, China; Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan Province, China
Jia-Yao Li
Department of Anesthesiology, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan Province, China; Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan Province, China
Li Liu
Department of Anesthesiology, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan Province, China; Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan Province, China
Jing Jia
Department of Anesthesiology, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan Province, China; Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan Province, China; Corresponding author. Department of Anesthesiology, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan Province, China.
Chronic obstructive pulmonary disease (COPD) and other respiratory diseases frequently present with airway mucus hypersecretion, which not only affects the patient's quality of life but also poses a constant threat to their life expectancy. Ubiquitin-specific protease 7 (USP7), a deubiquitinating enzyme, affects cell differentiation, tissue growth, and disease development. However, its role in airway mucus hypersecretion induced by COPD remains elusive. In this study, USP7 expression was significantly upregulated in airway epithelial samples from patients with COPD, and USP7 was also overexpressed in mouse lung and human airway epithelial cells in models of airway mucus hypersecretion. Inhibition of USP7 reduced the expression of nuclear factor kappa B (NF-κB), phosphorylated-NF-κB (p-NF-κB), and phosphonated inhibitor of nuclear factor kappa B (p-IκBα), and alleviated the airway mucus hypersecretion in vivo and in vitro. Further research revealed that USP7 stimulated airway mucus hypersecretion through the activation of NF-κB nuclear translocation. In addition, the expression of mucin 5AC (MUC5AC) was suppressed by the NF-κB inhibitor erdosteine. These findings suggest that USP7 stimulates the NF-κB signaling pathway, which promotes airway mucus hypersecretion. This study identifies one of the mechanisms regulating airway mucus secretion and provides a new potential target for its prevention and treatment.
