Smoking-associated increase in mucins 1 and 4 in human airways
|Author:||Merikallio, Heta1,2,3; Kaarteenaho, Riitta2,3; Lindén, Sara4;|
1Respiratory Medicine Unit, Department of Medicine Solna and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden
2Research Unit of Internal Medicine, University of Oulu, Oulu, Finland
3Medical Research Center Oulu, Oulu University Hospital, Oulu, Finland
4Department of Biomedical Chemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
5Department of Respiratory Medicine and Allergy, Karolinska University Hospital Solna, Stockholm, Sweden
6Department of Pathology, Center for Cancer Research and Translational Medicine, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
|Online Access:||PDF Full Text (PDF, 2.3 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe2020120399208
|Publish Date:|| 2020-12-03
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 sex-matched 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.
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
3121 General medicine, internal medicine and other clinical medicine
This work was supported by grants from the Foundation of the Finnish Anti-Tuberculosis Association, the Jalmari and Rauha Ahokas Foundation, the Swedish Heart-Lung Foundation, the Research Foundation of the Pulmonary Diseases, King Gustaf V’s and Queen Victoria’s Freemasons’ Foundation, Karolinska Institutet, The Swedish Research Council and through the Regional Agreement on Medical Training and Clinical Research (ALF) between Stockholm County Council and Karolinska Institutet. Dr. Chuan-Xing Li is the recipient of an ERS-EU RESPIRE2 MCF -2013.
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