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Increased Autophagy-Related 5 Gene Expression Is Associated with Collagen Expression in the Airways of Refractory
Audrey H Poon1, David F Choy2, Fazila Chouiali1
1Meakins-Christie Laboratories, Faculty of Medicine, McGill University, Montreal, QC, Canada.
Background:
Fibrosis, particularly excessive collagen deposition, presents a challenge for treating asthmatic individuals. At present, no drugs can remove or reduce excessive collagen in asthmatic airways. Hence, the identification of pathways involved in collagen deposition would help to generate therapeutic targets to interfere with the airway remodeling process. Autophagy, a cellular degradation process, has been shown to be dysregulated in various fibrotic diseases, and genetic association studies in independent human populations have identified autophagy-related 5 (ATG5) to be associated with asthma pathogenesis. Hence, the dysregulation of autophagy may contribute to fibrosis in asthmatic airways.
Objective:
This study aimed to determine if (1) collagen deposition in asthmatic airways is associated with ATG5 expression and (2) ATG5 protein expression is associated with asthma per se and severity.
Methods:
Gene expression of transforming growth factor beta 1, various asthma-related collagen types [collagen, type I, alpha 1; collagen, type II, alpha 1; collagen, type III, alpha 1; collagen, type V, alpha 1 (COL5A1) and collagen, type V, alpha 2], and ATG5 were measured using mRNA isolated from bronchial biopsies of refractory asthmatic subjects and assessed for pairwise associations. Protein expression of ATG5 in the airways was measured and associations were assessed for asthma per se, severity, and lung function.
Main Results:
In refractory asthmatic individuals, gene expression of ATG5 was positively associated with COL5A1 in the airways. No association was detected between ATG5 protein expression and asthma per se, severity, and lung function.
Conclusion And Clinical Relevance:
Positive correlation between the gene expression patterns of ATG5 and COL5A1 suggests that dysregulated autophagy may contribute to subepithelial fibrosis in the airways of refractory asthmatic individuals. This finding highlights the therapeutic potential of ATG5 in ameliorating airway remodeling in the difficult-to-treat refractory asthmatic individuals.
Insights
Autophagy gene ATG5 (autophagy-related 5) expression correlates with collagen gene COL5A1 in asthma, suggesting autophagy’s role in airway fibrosis. This points to ATG5 as a potential therapeutic target for difficult-to-treat asthma.
Area of Science:
- Pulmonary Medicine
- Cellular Biology
- Genetics
Background:
- Asthma involves airway fibrosis due to excessive collagen deposition, a challenge in treatment.
- Current therapies cannot reverse established airway collagen.
- Autophagy dysregulation is implicated in fibrotic diseases, with ATG5 (autophagy-related 5) linked to asthma.
Purpose of the Study:
- To investigate the association between collagen deposition and ATG5 expression in asthmatic airways.
- To determine if ATG5 protein levels correlate with asthma presence, severity, and lung function.
Main Methods:
- Gene expression of ATG5 and various collagen types (including COL5A1) was analyzed from bronchial biopsies of refractory asthmatics.
- Protein expression of ATG5 was measured in airway tissues.
- Associations were assessed between gene/protein expression and asthma parameters.
Main Results:
- A positive correlation was found between ATG5 gene expression and COL5A1 gene expression in the airways of refractory asthmatics.
- No significant association was observed between ATG5 protein expression and asthma, its severity, or lung function.
Conclusions:
- The correlation between ATG5 and COL5A1 gene expression suggests autophagy dysregulation contributes to airway fibrosis in refractory asthma.
- ATG5 presents a potential therapeutic target for managing airway remodeling in difficult-to-treat asthma patients.
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