title: Lyn regulates mucus secretion and MUC5AC via the STAT6 signaling pathway during allergic airway inflammation.
abstract: Hypersecretion of mucus is an important component of airway remodeling and contributes to the mucus plugs and airflow obstruction associated with severe asthma phenotypes. Lyn has been shown to down-regulate allergen-induced airway inflammation. However, the role of Lyn in mucin gene expression remains unresolved. In this study, we first demonstrate that Lyn overexpression decreased the mucus hypersecretion and levels of the muc5ac transcript in mice exposed to ovalbumin (OVA). Lyn overexpression also decreased the infiltration of inflammatory cells and the levels of IL-13 and IL-4 in OVA-challenged airways. Whereas Lyn knockdown increased the IL-4 or IL-13-induced MUC5AC transcript and protein levels in the human bronchial epithelial cell line, 16HBE, Lyn overexpression decreased IL-4- or IL-13-induced MUC5AC transcript and protein levels. Overexpression of Lyn also decreased the expression and phosphorylation of STAT6 in OVA-exposed mice, whereas Lyn knockdown increased STAT6 and MUC5AC levels in 16HBE cells. Finally, chromatin immunoprecipitation analysis confirmed that Lyn overexpression decreased the binding of STAT6 to the promoter region of Muc5ac in mice exposed to OVA. Collectively, these findings demonstrated that Lyn overexpression ameliorated airway mucus hypersecretion by down-regulating STAT6 and its binding to the MUC5AC promoter.
authors.affiliation: Inflammation &Allergic Diseases Research Unit, Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, China.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Wang
authors.affiliation: The First Clinic College, Chongqing Medical University, Chongqing 401331, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Li
authors.affiliation: Inflammation &Allergic Diseases Research Unit, Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, China.
authors.forename: Deyu
authors.initials: D
authors.lastname: Luo
authors.affiliation: Inflammation &Allergic Diseases Research Unit, Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Wang
authors.affiliation: Inflammation &Allergic Diseases Research Unit, Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, School of Medicine, Shenzhen University, Nanhai Ave 3688, Shenzhen Guangdong 518060, P.R. China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Liu
authors.affiliation: State Key Laboratories of Respiratory Disease, Ghuangzhou Medical University, Guangdong 510120, P.R. China.
authors.forename: Nanshan
authors.initials: N
authors.lastname: Zhong
authors.affiliation: Department of Basic Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, 501 N Columbia Rd, Grand Forks, ND 58203-9037, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Wu
authors.affiliation: Inflammation &Allergic Diseases Research Unit, Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, China.
authors.forename: Guoping
authors.initials: G
authors.lastname: Li
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D015870:Gene Expression; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D055271:Mucin 5AC / Q000235:genetics* / Q000378:metabolism; D009093:Mucus / Q000378:metabolism*; D010047:Ovalbumin / Q000276:immunology; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012130:Respiratory Hypersensitivity / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D050800:STAT6 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D019061:src-Family Kinases / Q000235:genetics* / Q000378:metabolism
chemical_list: D016207:Cytokines; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D010047:Ovalbumin; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases