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Investigating Autophagy as a Target in Asthma and Understanding How Autophagy Can Modulate Allergen-Induced Airway Remodelling
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Investigating Autophagy as a Target in Asthma and Understanding How Autophagy Can Modulate Allergen-Induced Airway Remodelling
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Dissertation
Investigating Autophagy as a Target in Asthma and Understanding How Autophagy Can Modulate Allergen-Induced Airway Remodelling
2021
Overview
Background:Airway remodelling is an untreatable hallmark of asthma. Autophagy, the cellular homeostatic recycling mechanism has emerged as a factor playing a role in asthma and potentially airway remodelling.Objectives:To explore the involvement of autophagy in asthmatic airway remodelling and test autophagy inhibition as a novel therapeutic target in asthmatics.Methodology:Autophagy protein expression was measured in the airways of both human and mouse asthmatic tissue by immunohistochemistry. Autophagy inhibitors chloroquine (CQ) and bafilomycin A1 (BafA1) were tested in murine asthma models. Relevant lung function, cell counts, histological staining and protein expression were supported by in vitroexperiments.Results:We have found increased autophagy protein expression involved in asthmatic airway remodelling in human and mice tissue. Transforming growth factor beta (TGF-β) concomitantly induces remodelling changes and the upregulation of autophagy. Autophagy inhibition reduced the pathophysiological symptoms of asthma.Conclusion:Autophagy contributes to airway remodelling in asthma and autophagy modulation is a promising approach in developing therapies that target remodelling.
Publisher
ProQuest Dissertations & Theses
Subject
ISBN
9798380498517
