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Increased autophagy-related 5 gene expression is associated with collagen expression in the airways of refractory asthmatics

Poon Audrey H., Choy David F., Chouiali Fazila, Ramakrishnan Rakhee K., Mahboub Bassam, Audusseau Severine, Mogas Andrea, Harris Jeffrey M., Arron Joseph R., Laprise Catherine et Hamid Qutayba. (2017). Increased autophagy-related 5 gene expression is associated with collagen expression in the airways of refractory asthmatics. Frontiers in Immunology, 8, (355), p. 1-8.

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URL officielle: http://dx.doi.org/doi:10.3389/fimmu.2017.00355

Résumé

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.

Type de document:Article publié dans une revue avec comité d'évaluation
ISSN:1664-3224
Volume:8
Numéro:355
Pages:p. 1-8
Version évaluée par les pairs:Oui
Date:2017
Identifiant unique:10.3389/fimmu.2017.00355
Sujets:Sciences de la santé > Sciences médicales > Génétique
Sciences de la santé > Sciences médicales > Immunologie
Département, module, service et unité de recherche:Départements et modules > Département des sciences fondamentales
Mots-clés:autophagy, ATG5, asthma, collagen, airway remodeling
Déposé le:26 avr. 2017 22:53
Dernière modification:26 avr. 2017 22:53
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