Characterization of a novel model incorporating airway epithelial damage and related fibrosis to the pathogenesis of asthma
Autor: | Simon G. Royce, Krupesh P. Patel, Chrishan S. Samuel |
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Rok vydání: | 2013 |
Předmět: |
Pathology
medicine.medical_specialty Ovalbumin Apoptosis Bronchi Biology Naphthalenes Epithelium Pathology and Forensic Medicine Epithelial Damage Pathogenesis Hydroxyproline chemistry.chemical_compound Mice Fibrosis Metaplasia medicine Animals Molecular Biology Lung Goblet cell Mice Inbred BALB C Cell Biology respiratory system medicine.disease Asthma respiratory tract diseases Disease Models Animal medicine.anatomical_structure chemistry biology.protein Female Collagen medicine.symptom Bronchial Hyperreactivity |
Zdroj: | Laboratory investigation; a journal of technical methods and pathology. 94(12) |
ISSN: | 1530-0307 |
Popis: | Asthma develops from injury to the airways/lungs, stemming from airway inflammation (AI) and airway remodeling (AWR), both contributing to airway hyperresponsiveness (AHR). Airway epithelial damage has been identified as a new etiology of asthma but is not targeted by current treatments. Furthermore, it is poorly studied in currently used animal models of AI and AWR. Therefore, this study aimed to incorporate epithelial damage/repair with the well-established ovalbumin (OVA)-induced model of chronic allergic airway disease (AAD), which presents with AI, AWR, and AHR, mimicking several features of human asthma. A 3-day naphthalene (NA)-induced model of epithelial damage/repair was superimposed onto the 9-week OVA-induced model of chronic AAD, before 6 weeks of OVA nebulization (NA+OVA group), during the second last OVA nebulization period (OVA/NA group) or 1 day after the 6-week OVA nebulization period (OVA+NA group), using 6-8-week-old female Balb/c mice (n=6-12/group). Mice subjected to the 9-week OVA model, 3-day NA model or respective vehicle treatments (saline and corn oil) were used as appropriate controls. OVA alone significantly increased epithelial thickness and apoptosis, goblet cell metaplasia, TGF-β1, subepithelial collagen (assessed by morphometric analyses of various histological stains), total lung collagen (hydroxyproline analysis), and AHR (invasive plethysmography) compared with that in saline-treated mice (all P |
Databáze: | OpenAIRE |
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