Smoking-associated increase in mucins 1 and 4 in human airways
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RESEARCH
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Smoking-associated increase in mucins 1 and 4 in human airways Heta Merikallio1,2,3*, Riitta Kaarteenaho2,3, Sara Lindén4, Médea Padra4, Reza Karimi1,5, Chuan-Xing Li1, Elisa Lappi-Blanco6, Åsa M. Wheelock1 and Magnus C. Sköld1,5
Abstract Rationale: Smoking-related chronic obstructive pulmonary disease (COPD) is associated with dysregulated production of mucus. Mucins (MUC) are important both for mucus secretion and epithelial defense. We have examined the distribution of MUC1 and MUC4 in the airway epithelial cells of never-smokers and smokers with and without COPD. Methods: Mucosal biopsies and bronchial wash samples were obtained by bronchoscopy from age- and sexmatched COPD-patients (n = 38; GOLD I-II/A-B), healthy never-smokers (n = 40) and current smokers with normal lung function (n = 40) from the Karolinska COSMIC cohort (NCT02627872). Cell-specific expressions of MUC1, MUC4 and regulating factors, i.e., epithelial growth factor receptor (EGFR) 1 and 2, were analyzed by immunohistochemistry. Soluble MUC1 was measured by quantitative immunodetection on slot blot. Results: The levels of cell-bound MUC1 expression in basal cells and in soluble MUC1 in bronchial wash were increased in smokers, regardless of airway obstruction. Patients with chronic bronchitis had higher MUC1 expression. The expression of MUC4 in cells with goblet cell phenotype was increased in smokers. The expression of EGFR2, but not that of EGFR1, was higher in never-smokers than in smokers. Conclusions: Smoking history and the presence of chronic bronchitis, regardless of airway obstruction, affect both cellular and soluble MUC1 in human airways. Therefore, MUC1 may be a novel marker for smoking- associated airway disease. Keywords: Bronchus, Epithelium, Mucin, Smoking, COPD, Chronic Bronchitis
Introduction The mucus layer on the top of the airway epithelium forms the first line of defense against pathogens, toxins and foreign particles [1]. Mucus binds and clears the pathogens through mucociliary clearance. However, abnormal mucus production and clearance can contribute to respiratory diseases such as chronic obstructive pulmonary disease (COPD) [2–4].
* Correspondence: [email protected] 1 Respiratory Medicine Unit, Department of Medicine Solna and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden 2 Research Unit of Internal Medicine, University of Oulu, Oulu, Finland Full list of author information is available at the end of the article
Mucin (MUC) macromolecules are believed to participate in the mucosal defense system by protecting the airway epithelium [5, 6]. Moreover, increased numbers of mucus producing cells i.e. hyperplasia of goblet cells, in the airway epithelium have been shown to associate with increased production of MUC [5]. MUCs are high molecular weight glycosylated proteins and are key components of most gel-like secretions [7]. Airway MUCs are major constituents of the secreted layer that comprise lung mucus in healthy airways and are a part of the mucociliary defens
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