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Autophagy is selectively activated and correlates with airway remodeling in asthma

McAlinden, KD, Deshpande, DA, Ghavami, S, Xenaki, D, Sohal, SS ORCID: 0000-0001-9627-6498, Oliver, BG, Haghi, M and Sharma, P 2019 , 'Autophagy is selectively activated and correlates with airway remodeling in asthma' , American Journal of Respiratory Cell and Molecular Biology, vol. 60, no. 5 , pp. 541-553 , doi: 10.1165/rcmb.2018-0169OC.

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Abstract

Current asthma therapies fail to target airway remodeling that correlates with asthma severity driving disease progression that ultimately leads to loss of lung function. Macroautophagy (hereinafter “autophagy”) is a fundamental cell-recycling mechanism in all eukaryotic cells; emerging evidence suggests that it is dysregulated in asthma. We investigated the interrelationship between autophagy and airway remodeling and assessed preclinical efficacy of a known autophagy inhibitor in murine models of asthma. Human asthmatic and nonasthmatic lung tissues were histologically evaluated and were immunostained for key autophagy markers. The percentage area of positive staining was quantified in the epithelium and airway smooth muscle bundles using ImageJ software. Furthermore, the autophagy inhibitor chloroquine was tested intranasally in prophylactic (3 wk) and treatment (5 wk) models of allergic asthma in mice. Human asthmatic tissues showed greater tissue inflammation and demonstrated hallmark features of airway remodeling, displaying thickened epithelium (P P  P P  P P  P  < 0.05), suggesting a potential role of ciliophagy in asthma. Murine asthma models demonstrated effective preclinical efficacy (reduced key features of allergic asthma: airway inflammation, airway hyperresponsiveness, and airway remodeling) of the autophagy inhibitor chloroquine. Our data demonstrate cell context–dependent and selective activation of autophagy in structural cells in asthma. Furthermore, this pathway can be effectively targeted to ameliorate airway remodeling in asthma.

Item Type: Article
Authors/Creators:McAlinden, KD and Deshpande, DA and Ghavami, S and Xenaki, D and Sohal, SS and Oliver, BG and Haghi, M and Sharma, P
Keywords: asthma, COPD, remodeling, autophagy, airways, epithelium, Beclin-1, immunohistochemistry
Journal or Publication Title: American Journal of Respiratory Cell and Molecular Biology
Publisher: American Thoracic Society
ISSN: 1535-4989
DOI / ID Number: 10.1165/rcmb.2018-0169OC
Copyright Information:

Copyright © 2019 by the American Thoracic Society

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