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Autophagy Activation in Asthma Airways Remodeling
Kielan D McAlinden1,2,3, Deepak A Deshpande4, Saeid Ghavami5
11 Graduate School of Health and.
American Journal of Respiratory Cell and Molecular Biology
|November 2, 2018
Summary
Current asthma treatments do not address airway remodeling. This study shows autophagy is dysregulated in asthma and inhibiting it with chloroquine reduces airway remodeling and inflammation in mice.
Area of Science:
- Cellular Biology
- Immunology
- Respiratory Medicine
Background:
- Current asthma therapies do not target airway remodeling, a key factor in disease progression and lung function loss.
- Macroautophagy (autophagy), a fundamental cellular process, appears dysregulated in asthma, suggesting a potential therapeutic target.
Purpose of the Study:
- To investigate the relationship between autophagy and airway remodeling in asthma.
- To evaluate the preclinical efficacy of an autophagy inhibitor, chloroquine, in murine asthma models.
Main Methods:
- Human asthmatic and nonasthmatic lung tissues were analyzed for histological features of airway remodeling and expression of autophagy markers (Beclin-1, ATG5, p62).
- Autophagy inhibition using chloroquine was tested in prophylactic and treatment models of allergic asthma in mice, assessing airway inflammation, hyperresponsiveness, and remodeling.
Main Results:
- Asthmatic human lung tissues exhibited significant airway remodeling, including thickened epithelium, increased lamina propria depth, and larger airway smooth muscle bundles.
- Higher expression of autophagy markers Beclin-1 and ATG5, and reduced p62, were observed in asthmatic tissues, with elevated Beclin-1 in epithelial and ciliated cells.
- Chloroquine treatment effectively reduced airway inflammation, hyperresponsiveness, and airway remodeling in murine asthma models.
Conclusions:
- Autophagy is selectively activated in structural cells in asthma in a context-dependent manner.
- Targeting the autophagy pathway with inhibitors like chloroquine shows promise for ameliorating airway remodeling in asthma.
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