MUC1 deficiency mediates corticosteroid resistance in chronic obstructive pulmonary disease
Authors: Julio Cortijo
Pilar Ribera
Sonia Contreras
Javier Milara
Inés Roger
Esteban Morcillo
Paula Montero
Lucía Díaz-Platas
Beatriz Ballester
Ángel Cogolludo
Journal: Respiratory Research (2018)
Discipline: CLINICAL MEDICINE
Keywords: Chronic obstructive pulmonary disease; Corticosteroid resistance; MUC1.
Affiliations: Department of Pharmacology, Faculty of Medicine, Jaume I University, Castellón de la Plana, Spain. ., Pharmacy Unit, University General Hospital Consortium, Valencia, Spain. ., CIBERES, Health Institute Carlos III, Valencia, Spain. ., Unidad de Investigación Clínica, Consorcio Hospital General Universitario, Avenida tres cruces s/n, E-46014, Valencia, Spain. ., Unidade Radiofármacos PET, GALARIA, Santiago de Compostela, A Coruña, Spain., Department of Pharmacology, Faculty of Medicine, University of Valencia, Valencia, Spain., CIBERES, Health Institute Carlos III, Valencia, Spain., Department of Pharmacology, School of Medicine, Universidad Complutense de Madrid, Madrid, Spain., Health Research Institute INCLIVA, Valencia, Spain., Research and teaching Unit, University General Hospital Consortium, Valencia, Spain.

Abstract:  Background: Lung 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. Methods: MUC1-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. Results: MUC1-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 &lt; 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. Conclusions: These results confirm a role for MUC1-CT mediating corticosteroid efficacy in COPD. 

Retracted: No

PubPeer comments:
 The Western blots and other figures in this paper have an interesting layout that appears to be shared with many other papers, as discussed in a January 2020 post on Leonid Schneider s blog: https: forbetterscience.com 2020 01 24 the-full-service-paper-mill-and-its-chinese-customers The list of these papers is available here: https: docs.google.com spreadsheets d 1KXqTAyl4j-jVorFPMD2XRpr76LcIKJ0CVyIvRj0exYQ edit?usp=sharing In almost all papers, Western blot panels within the same figure, and across figures and papers, appear to share the same background, while the bands are regularly spaced, all have similar rounded edges without the usual smudges and specks, and with some bands showing a recognizable  jumping sardine shape. Also in almost all papers, bar graphs show a characteristic layout with bars in solid shades of grey, and the left-most bar in black, as well as double-edged error bars. Many papers have  cell viability and  apoptotic cells graphs. To illustrate the recognizable layout of the graphs in this paper, here is Figure 2. ![file] ,