ArticleRespiratory research2018
MUC1 deficiency mediates corticosteroid resistance in chronic obstructive pulmonary disease.
Article in Respiratory research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 22 citations in OpenAlex.
- The role of immune cell crosstalk and signaling pathways in the pathogenesis of pulmonary fibrosis.Molecular biology reports · 2026Review
- MUC1 in the upper-lower airway inflammatory continuum: an endotype-centered perspective.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- MUC1 alleviates PM2.5-induced airway inflammation by inhibiting the IRAK4/NF-κB/NLRP3 mediated pyroptosis in airway epithelial cells.Frontiers in immunology · 2025Article
- CCL4 Affects Eosinophil Survival via the Shedding of the MUC1 N-Terminal Domain in Airway Inflammation.Cells · 2024Article
- cAMP-PDE signaling in COPD: Review of cellular, molecular and clinical features.Biochemistry and biophysics reports · 2023Review
- Expression of targets of the RNA-binding protein AUF-1 in human airway epithelium indicates its role in cellular senescence and inflammation.Frontiers in immunology · 2023Article
- The pan-JAK inhibitor LAS194046 reduces neutrophil activation from severe asthma and COPD patients in vitro.Scientific reports · 2022Article
- A New Immortalized Human Alveolar Epithelial Cell Model to Study Lung Injury and Toxicity on a Breathing Lung-On-Chip System.Frontiers in toxicology · 2022Article
- Membrane-associated mucins of the human ocular surface in health and disease.The ocular surface · 2021Review
- Corticosteroid Resistance in Smokers-A Substudy Analysis of the CORTICO-COP Randomised Controlled Trial.Journal of clinical medicine · 2021Article
- The role of mucin 1 in respiratory diseases.European respiratory review : an official journal of the European Respiratory Society · 2021Review
- Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundLung inflammation in COPD is poorly controlled by inhaled corticosteroids (ICS). Strategies to improve ICS efficacy or the search of biomarkers who may select those patients candidates to receive ICS in COPD are needed. Recent data indicate that MUC1 cytoplasmic tail (CT) membrane mucin can mediate corticosteroid efficacy in chronic rhinosinusitis. The objective of this work was to analyze the previously unexplored role of MUC1 on corticosteroid efficacy in COPD in vitro and in vivo models.
methodsMUC1-CT expression was measured by real time PCR, western blot, immunohistochemistry and immunofluorescence. The inflammatory mediators IL-8, MMP9, GM-CSF and MIP3α were measured by ELISA. The effect of MUC1 on inflammation and corticosteroid anti-inflammatory effects was measured using cell siRNA in vitro and Muc1-KO in vivo animal models.
resultsMUC1-CT expression was downregulated in lung tissue, bronchial epithelial cells and lung neutrophils from smokers (n = 11) and COPD (n = 11) patients compared with healthy subjects (n = 10). MUC1 was correlated with FEV1% (ρ = 0.7479; p < 0.0001) in smokers and COPD patients. Cigarette smoke extract (CSE) decreased the expression of MUC1 and induced corticosteroid resistance in human primary bronchial epithelial cells and human neutrophils. MUC1 Gene silencing using siRNA-MUC1 impaired the anti-inflammatory effects of dexamethasone and reduced glucocorticoid response element activation. Dexamethasone promoted glucocorticoid receptor alpha (GRα) and MUC1-CT nuclear translocation and co-localization that was inhibited by CSE. Lung function decline and inflammation induced by lipopolysaccharide and cigarette smoke in Muc1 KO mice was resistant to dexamethasone.
conclusionsThese results confirm a role for MUC1-CT mediating corticosteroid efficacy in COPD.
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