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Published in: Respiratory Research 1/2020

01-12-2020 | Bronchitis | Research

Smoking-associated increase in mucins 1 and 4 in human airways

Authors: Heta Merikallio, Riitta Kaarteenaho, Sara Lindén, Médea Padra, Reza Karimi, Chuan-Xing Li, Elisa Lappi-Blanco, Åsa M. Wheelock, Magnus C. Sköld

Published in: Respiratory Research | Issue 1/2020

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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 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.
Appendix
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Literature
1.
go back to reference Zhou-Suckow Z, Duerr J, Hagner M, Agrawal R, Mall MA. Airway mucus, inflammation and remodeling: emerging links in the pathogenesis of chronic lung diseases. Cell Tissue Res. 2017;367(3):537–50.CrossRefPubMed Zhou-Suckow Z, Duerr J, Hagner M, Agrawal R, Mall MA. Airway mucus, inflammation and remodeling: emerging links in the pathogenesis of chronic lung diseases. Cell Tissue Res. 2017;367(3):537–50.CrossRefPubMed
2.
go back to reference Kesimer M, Ford AA, Ceppe A, Radicioni G, Cao R, Davis CW, et al. Airway Mucin Concentration as a Marker of Chronic Bronchitis. N Engl J Med. 2017;377(10):911–22.PubMedPubMedCentralCrossRef Kesimer M, Ford AA, Ceppe A, Radicioni G, Cao R, Davis CW, et al. Airway Mucin Concentration as a Marker of Chronic Bronchitis. N Engl J Med. 2017;377(10):911–22.PubMedPubMedCentralCrossRef
3.
4.
go back to reference Wedzicha JA. Airway Mucins in Chronic Obstructive Pulmonary Disease. N Engl J Med. 2017;377(10):986–7.CrossRefPubMed Wedzicha JA. Airway Mucins in Chronic Obstructive Pulmonary Disease. N Engl J Med. 2017;377(10):986–7.CrossRefPubMed
5.
go back to reference Corfield AP. Mucins: a biologically relevant glycan barrier in mucosal protection. Biochim Biophys Acta. 2015;1850(1):236–52.CrossRefPubMed Corfield AP. Mucins: a biologically relevant glycan barrier in mucosal protection. Biochim Biophys Acta. 2015;1850(1):236–52.CrossRefPubMed
6.
go back to reference Rose MC, Voynow JA. Respiratory tract mucin genes and mucin glycoproteins in health and disease. Physiol Rev. 2006;86(1):245–78.CrossRefPubMed Rose MC, Voynow JA. Respiratory tract mucin genes and mucin glycoproteins in health and disease. Physiol Rev. 2006;86(1):245–78.CrossRefPubMed
7.
go back to reference Ramsey KA, Rushton ZL, Ehre C. Mucin Agarose Gel Electrophoresis: Western Blotting for High-molecular-weight Glycoproteins. J Vis Exp. 2016;(112):54153. Ramsey KA, Rushton ZL, Ehre C. Mucin Agarose Gel Electrophoresis: Western Blotting for High-molecular-weight Glycoproteins. J Vis Exp. 2016;(112):54153.
8.
go back to reference Rose MC, Nickola TJ, Voynow JA. Airway mucus obstruction: mucin glycoproteins, MUC gene regulation and goblet cell hyperplasia. Am J Respir Cell Mol Biol. 2001;25(5):533–7.CrossRefPubMed Rose MC, Nickola TJ, Voynow JA. Airway mucus obstruction: mucin glycoproteins, MUC gene regulation and goblet cell hyperplasia. Am J Respir Cell Mol Biol. 2001;25(5):533–7.CrossRefPubMed
9.
go back to reference Bafna S, Kaur S, Batra SK. Membrane-bound mucins: the mechanistic basis for alterations in the growth and survival of cancer cells. Oncogene. 2010;29(20):2893–904.PubMedPubMedCentralCrossRef Bafna S, Kaur S, Batra SK. Membrane-bound mucins: the mechanistic basis for alterations in the growth and survival of cancer cells. Oncogene. 2010;29(20):2893–904.PubMedPubMedCentralCrossRef
10.
go back to reference Hattrup CL, Gendler SJ. Structure and function of the cell surface (tethered) mucins. Annu Rev Physiol. 2008;70:431–57.CrossRefPubMed Hattrup CL, Gendler SJ. Structure and function of the cell surface (tethered) mucins. Annu Rev Physiol. 2008;70:431–57.CrossRefPubMed
12.
go back to reference Engelmann K, Kinlough CL, Muller S, Razawi H, Baldus SE, Hughey RP, et al. Transmembrane and secreted MUC1 probes show trafficking-dependent changes in O-glycan core profiles. Glycobiology. 2005;15(11):1111–24.CrossRefPubMed Engelmann K, Kinlough CL, Muller S, Razawi H, Baldus SE, Hughey RP, et al. Transmembrane and secreted MUC1 probes show trafficking-dependent changes in O-glycan core profiles. Glycobiology. 2005;15(11):1111–24.CrossRefPubMed
13.
go back to reference Linden SK, Sheng YH, Every AL, Miles KM, Skoog EC, Florin TH, et al. MUC1 limits Helicobacter pylori infection both by steric hindrance and by acting as a releasable decoy. PLoS Pathog. 2009;5(10):e1000617.PubMedPubMedCentralCrossRef Linden SK, Sheng YH, Every AL, Miles KM, Skoog EC, Florin TH, et al. MUC1 limits Helicobacter pylori infection both by steric hindrance and by acting as a releasable decoy. PLoS Pathog. 2009;5(10):e1000617.PubMedPubMedCentralCrossRef
14.
go back to reference Lapperre TS, Sont JK, van Schadewijk A, Gosman MM, Postma DS, Bajema IM, et al. Smoking cessation and bronchial epithelial remodelling in COPD: a cross-sectional study. Respir Res. 2007;8:85.PubMedPubMedCentralCrossRef Lapperre TS, Sont JK, van Schadewijk A, Gosman MM, Postma DS, Bajema IM, et al. Smoking cessation and bronchial epithelial remodelling in COPD: a cross-sectional study. Respir Res. 2007;8:85.PubMedPubMedCentralCrossRef
15.
go back to reference O'Donnell RA, Richter A, Ward J, Angco G, Mehta A, Rousseau K, et al. Expression of ErbB receptors and mucins in the airways of long term current smokers. Thorax. 2004;59(12):1032–40.PubMedPubMedCentralCrossRef O'Donnell RA, Richter A, Ward J, Angco G, Mehta A, Rousseau K, et al. Expression of ErbB receptors and mucins in the airways of long term current smokers. Thorax. 2004;59(12):1032–40.PubMedPubMedCentralCrossRef
16.
go back to reference Takeyama K, Jung B, Shim JJ, Burgel PR, Dao-Pick T, Ueki IF, et al. Activation of epidermal growth factor receptors is responsible for mucin synthesis induced by cigarette smoke. Am J Physiol Lung Cell Mol Physiol. 2001;280(1):L165–72.CrossRefPubMed Takeyama K, Jung B, Shim JJ, Burgel PR, Dao-Pick T, Ueki IF, et al. Activation of epidermal growth factor receptors is responsible for mucin synthesis induced by cigarette smoke. Am J Physiol Lung Cell Mol Physiol. 2001;280(1):L165–72.CrossRefPubMed
17.
go back to reference Patton S, Gendler SJ, Spicer AP. The epithelial mucin, MUC1, of milk, mammary gland and other tissues. Biochim Biophys Acta. 1995;1241(3):407–23.CrossRefPubMed Patton S, Gendler SJ, Spicer AP. The epithelial mucin, MUC1, of milk, mammary gland and other tissues. Biochim Biophys Acta. 1995;1241(3):407–23.CrossRefPubMed
18.
go back to reference Lappi-Blanco E, Makinen JM, Lehtonen S, Karvonen H, Sormunen R, Laitakari K, et al. Mucin-1 correlates with survival, smoking status, and growth patterns in lung adenocarcinoma. Tumour Biol. 2016;37(10):13811–20.CrossRefPubMed Lappi-Blanco E, Makinen JM, Lehtonen S, Karvonen H, Sormunen R, Laitakari K, et al. Mucin-1 correlates with survival, smoking status, and growth patterns in lung adenocarcinoma. Tumour Biol. 2016;37(10):13811–20.CrossRefPubMed
20.
go back to reference Chaturvedi P, Singh AP, Chakraborty S, Chauhan SC, Bafna S, Meza JL, et al. MUC4 mucin interacts with and stabilizes the HER2 oncoprotein in human pancreatic cancer cells. Cancer Res. 2008;68(7):2065–70.PubMedPubMedCentralCrossRef Chaturvedi P, Singh AP, Chakraborty S, Chauhan SC, Bafna S, Meza JL, et al. MUC4 mucin interacts with and stabilizes the HER2 oncoprotein in human pancreatic cancer cells. Cancer Res. 2008;68(7):2065–70.PubMedPubMedCentralCrossRef
21.
go back to reference Balgoma D, Yang M, Sjodin M, Snowden S, Karimi R, Levanen B, et al. Linoleic acid-derived lipid mediators increase in a female-dominated subphenotype of COPD. Eur Respir J. 2016;47(6):1645–56.CrossRefPubMed Balgoma D, Yang M, Sjodin M, Snowden S, Karimi R, Levanen B, et al. Linoleic acid-derived lipid mediators increase in a female-dominated subphenotype of COPD. Eur Respir J. 2016;47(6):1645–56.CrossRefPubMed
22.
go back to reference Forsslund H, Yang M, Mikko M, Karimi R, Nyren S, Engvall B, et al. Gender differences in the T-cell profiles of the airways in COPD patients associated with clinical phenotypes. Int J Chron Obstruct Pulmon Dis. 2017;12:35–48.CrossRefPubMed Forsslund H, Yang M, Mikko M, Karimi R, Nyren S, Engvall B, et al. Gender differences in the T-cell profiles of the airways in COPD patients associated with clinical phenotypes. Int J Chron Obstruct Pulmon Dis. 2017;12:35–48.CrossRefPubMed
23.
go back to reference Naz S, Kolmert J, Yang M, Reinke SN, Kamleh MA, Snowden S, et al. Metabolomics analysis identifies sex-associated metabotypes of oxidative stress and the autotaxin-lysoPA axis in COPD. Eur Respir J. 2017;49(6):1602322. Naz S, Kolmert J, Yang M, Reinke SN, Kamleh MA, Snowden S, et al. Metabolomics analysis identifies sex-associated metabotypes of oxidative stress and the autotaxin-lysoPA axis in COPD. Eur Respir J. 2017;49(6):1602322.
24.
go back to reference Karimi R, Tornling G, Forsslund H, Mikko M, Wheelock A, Nyren S, et al. Lung density on high resolution computer tomography (HRCT) reflects degree of inflammation in smokers. Respir Res. 2014;15:23.PubMedPubMedCentralCrossRef Karimi R, Tornling G, Forsslund H, Mikko M, Wheelock A, Nyren S, et al. Lung density on high resolution computer tomography (HRCT) reflects degree of inflammation in smokers. Respir Res. 2014;15:23.PubMedPubMedCentralCrossRef
25.
go back to reference Kohler M, Sandberg A, Kjellqvist S, Thomas A, Karimi R, Nyren S, et al. Gender differences in the bronchoalveolar lavage cell proteome of patients with chronic obstructive pulmonary disease. J Allergy Clin Immunol. 2013;131(3):743–51.CrossRefPubMed Kohler M, Sandberg A, Kjellqvist S, Thomas A, Karimi R, Nyren S, et al. Gender differences in the bronchoalveolar lavage cell proteome of patients with chronic obstructive pulmonary disease. J Allergy Clin Immunol. 2013;131(3):743–51.CrossRefPubMed
26.
go back to reference Yang M, Kohler M, Heyder T, Forsslund H, Garberg HK, Karimi R, et al. Long-term smoking alters abundance of over half of the proteome in bronchoalveolar lavage cell in smokers with normal spirometry, with effects on molecular pathways associated with COPD. Respir Res. 2018;19(1):40.PubMedPubMedCentralCrossRef Yang M, Kohler M, Heyder T, Forsslund H, Garberg HK, Karimi R, et al. Long-term smoking alters abundance of over half of the proteome in bronchoalveolar lavage cell in smokers with normal spirometry, with effects on molecular pathways associated with COPD. Respir Res. 2018;19(1):40.PubMedPubMedCentralCrossRef
27.
go back to reference Yang M, Kohler M, Heyder T, Forsslund H, Garberg HK, Karimi R, et al. Proteomic profiling of lung immune cells reveals dysregulation of phagocytotic pathways in female-dominated molecular COPD phenotype. Respir Res. 2018;19(1):39.PubMedPubMedCentralCrossRef Yang M, Kohler M, Heyder T, Forsslund H, Garberg HK, Karimi R, et al. Proteomic profiling of lung immune cells reveals dysregulation of phagocytotic pathways in female-dominated molecular COPD phenotype. Respir Res. 2018;19(1):39.PubMedPubMedCentralCrossRef
28.
go back to reference Mikko M, Forsslund H, Cui L, Grunewald J, Wheelock AM, Wahlstrom J, et al. Increased intraepithelial (CD103+) CD8+ T cells in the airways of smokers with and without chronic obstructive pulmonary disease. Immunobiology. 2013;218(2):225–31.CrossRefPubMed Mikko M, Forsslund H, Cui L, Grunewald J, Wheelock AM, Wahlstrom J, et al. Increased intraepithelial (CD103+) CD8+ T cells in the airways of smokers with and without chronic obstructive pulmonary disease. Immunobiology. 2013;218(2):225–31.CrossRefPubMed
29.
go back to reference Naz S, Bhat M, Stahl S, Forsslund H, Skold CM, Wheelock AM, et al. Dysregulation of the Tryptophan Pathway Evidences Gender Differences in COPD. Metabolites. 2019;9(10):212. Naz S, Bhat M, Stahl S, Forsslund H, Skold CM, Wheelock AM, et al. Dysregulation of the Tryptophan Pathway Evidences Gender Differences in COPD. Metabolites. 2019;9(10):212.
30.
go back to reference Li CX, Wheelock CE, Skold CM, Wheelock AM. Integration of multi-omics datasets enables molecular classification of COPD. Eur Respir J. 2018;51(5):1701930. Li CX, Wheelock CE, Skold CM, Wheelock AM. Integration of multi-omics datasets enables molecular classification of COPD. Eur Respir J. 2018;51(5):1701930.
31.
go back to reference Sandberg A, Skold CM, Grunewald J, Eklund A, Wheelock AM. Assessing recent smoking status by measuring exhaled carbon monoxide levels. PLoS One. 2011;6(12):e28864.PubMedPubMedCentralCrossRef Sandberg A, Skold CM, Grunewald J, Eklund A, Wheelock AM. Assessing recent smoking status by measuring exhaled carbon monoxide levels. PLoS One. 2011;6(12):e28864.PubMedPubMedCentralCrossRef
32.
go back to reference al S-HCHe. Definition and classification of chronic bronchitis for clinical and epidemiological purposes. A report to the Medical Research Council by their Committee on the Aetiology of Chronic Bronchitis. Lancet. 1965;1(7389):775–779. al S-HCHe. Definition and classification of chronic bronchitis for clinical and epidemiological purposes. A report to the Medical Research Council by their Committee on the Aetiology of Chronic Bronchitis. Lancet. 1965;1(7389):775–779.
33.
go back to reference Forsslund H, Mikko M, Karimi R, Grunewald J, Wheelock AM, Wahlstrom J, et al. Distribution of T-cell subsets in BAL fluid of patients with mild to moderate COPD depends on current smoking status and not airway obstruction. Chest. 2014;145(4):711–22.CrossRefPubMed Forsslund H, Mikko M, Karimi R, Grunewald J, Wheelock AM, Wahlstrom J, et al. Distribution of T-cell subsets in BAL fluid of patients with mild to moderate COPD depends on current smoking status and not airway obstruction. Chest. 2014;145(4):711–22.CrossRefPubMed
34.
go back to reference Lofdahl JM, Cederlund K, Nathell L, Eklund A, Skold CM. Bronchoalveolar lavage in COPD: fluid recovery correlates with the degree of emphysema. Eur Respir J. 2005;25(2):275–81.CrossRefPubMed Lofdahl JM, Cederlund K, Nathell L, Eklund A, Skold CM. Bronchoalveolar lavage in COPD: fluid recovery correlates with the degree of emphysema. Eur Respir J. 2005;25(2):275–81.CrossRefPubMed
35.
go back to reference Karimi R, Tornling G, Grunewald J, Eklund A, Skold CM. Cell recovery in bronchoalveolar lavage fluid in smokers is dependent on cumulative smoking history. PLoS One. 2012;7(3):e34232.PubMedPubMedCentralCrossRef Karimi R, Tornling G, Grunewald J, Eklund A, Skold CM. Cell recovery in bronchoalveolar lavage fluid in smokers is dependent on cumulative smoking history. PLoS One. 2012;7(3):e34232.PubMedPubMedCentralCrossRef
36.
go back to reference Lee HJ, Xu X, Choe G, Chung DH, Seo JW, Lee JH, et al. Protein overexpression and gene amplification of epidermal growth factor receptor in nonsmall cell lung carcinomas: Comparison of four commercially available antibodies by immunohistochemistry and fluorescence in situ hybridization study. Lung Cancer. 2010;68(3):375–82.CrossRefPubMed Lee HJ, Xu X, Choe G, Chung DH, Seo JW, Lee JH, et al. Protein overexpression and gene amplification of epidermal growth factor receptor in nonsmall cell lung carcinomas: Comparison of four commercially available antibodies by immunohistochemistry and fluorescence in situ hybridization study. Lung Cancer. 2010;68(3):375–82.CrossRefPubMed
37.
go back to reference Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics. 1977;33(1):159–74.CrossRefPubMed Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics. 1977;33(1):159–74.CrossRefPubMed
38.
go back to reference Macao B, Johansson DG, Hansson GC, Hard T. Autoproteolysis coupled to protein folding in the SEA domain of the membrane-bound MUC1 mucin. Nat Struct Mol Biol. 2006;13(1):71–6.CrossRefPubMed Macao B, Johansson DG, Hansson GC, Hard T. Autoproteolysis coupled to protein folding in the SEA domain of the membrane-bound MUC1 mucin. Nat Struct Mol Biol. 2006;13(1):71–6.CrossRefPubMed
39.
go back to reference McAuley JL, Linden SK, Png CW, King RM, Pennington HL, Gendler SJ, et al. MUC1 cell surface mucin is a critical element of the mucosal barrier to infection. J Clin Invest. 2007;117(8):2313–24.PubMedPubMedCentralCrossRef McAuley JL, Linden SK, Png CW, King RM, Pennington HL, Gendler SJ, et al. MUC1 cell surface mucin is a critical element of the mucosal barrier to infection. J Clin Invest. 2007;117(8):2313–24.PubMedPubMedCentralCrossRef
40.
go back to reference Caramori G, Casolari P, Di Gregorio C, Saetta M, Baraldo S, Boschetto P, et al. MUC5AC expression is increased in bronchial submucosal glands of stable COPD patients. Histopathology. 2009;55(3):321–31.CrossRefPubMed Caramori G, Casolari P, Di Gregorio C, Saetta M, Baraldo S, Boschetto P, et al. MUC5AC expression is increased in bronchial submucosal glands of stable COPD patients. Histopathology. 2009;55(3):321–31.CrossRefPubMed
41.
go back to reference Kovalenko S, Dorofieiev A. The content of mucin MUC-2, −3 and −4 antigens in the bronchial mucosa membrane of chronic obstructive pulmonary disease patients during acute exacerbation - initial report. Adv Respir Med. 2017;85(1):3–7.CrossRefPubMed Kovalenko S, Dorofieiev A. The content of mucin MUC-2, −3 and −4 antigens in the bronchial mucosa membrane of chronic obstructive pulmonary disease patients during acute exacerbation - initial report. Adv Respir Med. 2017;85(1):3–7.CrossRefPubMed
42.
go back to reference Ishikawa N, Mazur W, Toljamo T, Vuopala K, Ronty M, Horimasu Y, et al. Ageing and long-term smoking affects KL-6 levels in the lung, induced sputum and plasma. BMC Pulm Med. 2011;11:22.PubMedPubMedCentralCrossRef Ishikawa N, Mazur W, Toljamo T, Vuopala K, Ronty M, Horimasu Y, et al. Ageing and long-term smoking affects KL-6 levels in the lung, induced sputum and plasma. BMC Pulm Med. 2011;11:22.PubMedPubMedCentralCrossRef
43.
go back to reference Zheng Z, Qi Y, Xu X, Jiang H, Li Z, Yang Q, et al. Sputum mucin 1 is increased during the acute phase of chronic obstructive pulmonary disease exacerbation. J Thorac Dis. 2017;9(7):1873–82.PubMedPubMedCentralCrossRef Zheng Z, Qi Y, Xu X, Jiang H, Li Z, Yang Q, et al. Sputum mucin 1 is increased during the acute phase of chronic obstructive pulmonary disease exacerbation. J Thorac Dis. 2017;9(7):1873–82.PubMedPubMedCentralCrossRef
44.
go back to reference Ishizaka A, Matsuda T, Albertine KH, Koh H, Tasaka S, Hasegawa N, et al. Elevation of KL-6, a lung epithelial cell marker, in plasma and epithelial lining fluid in acute respiratory distress syndrome. Am J Physiol Lung Cell Mol Physiol. 2004;286(6):L1088–94.CrossRefPubMed Ishizaka A, Matsuda T, Albertine KH, Koh H, Tasaka S, Hasegawa N, et al. Elevation of KL-6, a lung epithelial cell marker, in plasma and epithelial lining fluid in acute respiratory distress syndrome. Am J Physiol Lung Cell Mol Physiol. 2004;286(6):L1088–94.CrossRefPubMed
45.
go back to reference Shigemura M, Nasuhara Y, Konno S, Shimizu C, Matsuno K, Yamguchi E, et al. Effects of molecular structural variants on serum Krebs von den Lungen-6 levels in sarcoidosis. J Transl Med. 2012;10:111.PubMedPubMedCentralCrossRef Shigemura M, Nasuhara Y, Konno S, Shimizu C, Matsuno K, Yamguchi E, et al. Effects of molecular structural variants on serum Krebs von den Lungen-6 levels in sarcoidosis. J Transl Med. 2012;10:111.PubMedPubMedCentralCrossRef
46.
go back to reference Nathani N, Perkins GD, Tunnicliffe W, Murphy N, Manji M, Thickett DR. Kerbs von Lungren 6 antigen is a marker of alveolar inflammation but not of infection in patients with acute respiratory distress syndrome. Crit Care. 2008;12(1):R12.PubMedPubMedCentralCrossRef Nathani N, Perkins GD, Tunnicliffe W, Murphy N, Manji M, Thickett DR. Kerbs von Lungren 6 antigen is a marker of alveolar inflammation but not of infection in patients with acute respiratory distress syndrome. Crit Care. 2008;12(1):R12.PubMedPubMedCentralCrossRef
47.
go back to reference Tomita M, Ayabe T, Chosa E, Nose N, Nakamura K. Prognostic significance of preoperative serum Krebs von den Lungen-6 level in non-small cell lung cancer. Gen Thorac Cardiovasc Surg. 2016;64(11):657–61.CrossRefPubMed Tomita M, Ayabe T, Chosa E, Nose N, Nakamura K. Prognostic significance of preoperative serum Krebs von den Lungen-6 level in non-small cell lung cancer. Gen Thorac Cardiovasc Surg. 2016;64(11):657–61.CrossRefPubMed
48.
go back to reference Xu T, Li D, Wang H, Zheng T, Wang G, Xin Y. MUC1 downregulation inhibits non-small cell lung cancer progression in human cell lines. Exp Ther Med. 2017;14(5):4443–7.PubMedPubMedCentral Xu T, Li D, Wang H, Zheng T, Wang G, Xin Y. MUC1 downregulation inhibits non-small cell lung cancer progression in human cell lines. Exp Ther Med. 2017;14(5):4443–7.PubMedPubMedCentral
49.
go back to reference Schilders KA, Eenjes E, van Riet S, Poot AA, Stamatialis D, Truckenmuller R, et al. Regeneration of the lung: Lung stem cells and the development of lung mimicking devices. Respir Res. 2016;17:44.PubMedPubMedCentralCrossRef Schilders KA, Eenjes E, van Riet S, Poot AA, Stamatialis D, Truckenmuller R, et al. Regeneration of the lung: Lung stem cells and the development of lung mimicking devices. Respir Res. 2016;17:44.PubMedPubMedCentralCrossRef
50.
go back to reference Caramori G, Di Gregorio C, Carlstedt I, Casolari P, Guzzinati I, Adcock IM, et al. Mucin expression in peripheral airways of patients with chronic obstructive pulmonary disease. Histopathology. 2004;45(5):477–84.CrossRefPubMed Caramori G, Di Gregorio C, Carlstedt I, Casolari P, Guzzinati I, Adcock IM, et al. Mucin expression in peripheral airways of patients with chronic obstructive pulmonary disease. Histopathology. 2004;45(5):477–84.CrossRefPubMed
51.
go back to reference Aryal S, Diaz-Guzman E, Mannino DM. COPD and gender differences: an update. Transl Res. 2013;162(4):208–18.CrossRefPubMed Aryal S, Diaz-Guzman E, Mannino DM. COPD and gender differences: an update. Transl Res. 2013;162(4):208–18.CrossRefPubMed
52.
go back to reference Bitler BG, Goverdhan A, Schroeder JA. MUC1 regulates nuclear localization and function of the epidermal growth factor receptor. J Cell Sci. 2010;123(Pt 10):1716–23.PubMedPubMedCentralCrossRef Bitler BG, Goverdhan A, Schroeder JA. MUC1 regulates nuclear localization and function of the epidermal growth factor receptor. J Cell Sci. 2010;123(Pt 10):1716–23.PubMedPubMedCentralCrossRef
53.
go back to reference Anagnostis A, Neofytou E, Soulitzis N, Kampas D, Drositis I, Dermitzaki D, et al. Molecular profiling of EGFR family in chronic obstructive pulmonary disease: correlation with airway obstruction. Eur J Clin Investig. 2013;43(12):1299–306.CrossRef Anagnostis A, Neofytou E, Soulitzis N, Kampas D, Drositis I, Dermitzaki D, et al. Molecular profiling of EGFR family in chronic obstructive pulmonary disease: correlation with airway obstruction. Eur J Clin Investig. 2013;43(12):1299–306.CrossRef
54.
go back to reference de Boer WI, Hau CM, van Schadewijk A, Stolk J, van Krieken JHJM, Hiemstra PS. Expression of Epidermal Growth Factors and Their Receptors in the Bronchial Epithelium of Subjects With Chronic Obstructive Pulmonary Disease. Am J Clin Pathol. 2006;125(2):184–92.CrossRefPubMed de Boer WI, Hau CM, van Schadewijk A, Stolk J, van Krieken JHJM, Hiemstra PS. Expression of Epidermal Growth Factors and Their Receptors in the Bronchial Epithelium of Subjects With Chronic Obstructive Pulmonary Disease. Am J Clin Pathol. 2006;125(2):184–92.CrossRefPubMed
55.
go back to reference Suzuki M, Wada H, Yoshino M, Tian L, Shigematsu H, Suzuki H, et al. Molecular characterization of chronic obstructive pulmonary disease-related non-small cell lung cancer through aberrant methylation and alterations of EGFR signaling. Ann Surg Oncol. 2010;17(3):878–88.CrossRefPubMed Suzuki M, Wada H, Yoshino M, Tian L, Shigematsu H, Suzuki H, et al. Molecular characterization of chronic obstructive pulmonary disease-related non-small cell lung cancer through aberrant methylation and alterations of EGFR signaling. Ann Surg Oncol. 2010;17(3):878–88.CrossRefPubMed
56.
go back to reference Woodruff PG, Wolff M, Hohlfeld JM, Krug N, Dransfield MT, Sutherland ER, et al. Safety and efficacy of an inhaled epidermal growth factor receptor inhibitor (BIBW 2948 BS) in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2010;181(5):438–45.CrossRefPubMed Woodruff PG, Wolff M, Hohlfeld JM, Krug N, Dransfield MT, Sutherland ER, et al. Safety and efficacy of an inhaled epidermal growth factor receptor inhibitor (BIBW 2948 BS) in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2010;181(5):438–45.CrossRefPubMed
57.
go back to reference Karg A, Dinc ZA, Basok O, Ucvet A. MUC4 expression and its relation to ErbB2 expression, apoptosis, proliferation, differentiation, and tumor stage in non-small cell lung cancer (NSCLC). Pathol Res Pract. 2006;202(8):577–83.CrossRefPubMed Karg A, Dinc ZA, Basok O, Ucvet A. MUC4 expression and its relation to ErbB2 expression, apoptosis, proliferation, differentiation, and tumor stage in non-small cell lung cancer (NSCLC). Pathol Res Pract. 2006;202(8):577–83.CrossRefPubMed
58.
go back to reference Yang M, Kohler M, Heyder T, Forsslund H, Garberg HK, Karimi R, et al. Proteomic profiling of lung immune cells reveals dysregulation of phagocytotic pathways in female-dominated molecular COPD phenotype. Respiratory Research. 2018. In press. Yang M, Kohler M, Heyder T, Forsslund H, Garberg HK, Karimi R, et al. Proteomic profiling of lung immune cells reveals dysregulation of phagocytotic pathways in female-dominated molecular COPD phenotype. Respiratory Research. 2018. In press.
59.
go back to reference Zaretsky JZ, Barnea I, Aylon Y, Gorivodsky M, Wreschner DH, Keydar I. MUC1 gene overexpressed in breast cancer: structure and transcriptional activity of the MUC1 promoter and role of estrogen receptor alpha (ERalpha) in regulation of the MUC1 gene expression. Mol Cancer. 2006;5:57.PubMedPubMedCentralCrossRef Zaretsky JZ, Barnea I, Aylon Y, Gorivodsky M, Wreschner DH, Keydar I. MUC1 gene overexpressed in breast cancer: structure and transcriptional activity of the MUC1 promoter and role of estrogen receptor alpha (ERalpha) in regulation of the MUC1 gene expression. Mol Cancer. 2006;5:57.PubMedPubMedCentralCrossRef
Metadata
Title
Smoking-associated increase in mucins 1 and 4 in human airways
Authors
Heta Merikallio
Riitta Kaarteenaho
Sara Lindén
Médea Padra
Reza Karimi
Chuan-Xing Li
Elisa Lappi-Blanco
Åsa M. Wheelock
Magnus C. Sköld
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2020
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/s12931-020-01498-7

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