Wang, K and Le Crast, T and Larcombe, A and Zosky, GR and James, A and Noble, P, A Mouse Model of Asthma, Respirology, 4-9 April, 2014, Adelaide, Australia ISSN 1323-7799 (2014) [Conference Extract]
Introduction: Mouse models show that prolonged transforming growth factor alpha (TGFα) expression promotes chronic lung disease particularly in early growth response-1 (Egr-1) deficient mice. Notably, airway smooth muscle (ASM) is thickened and the exaggerated increase in lung resistance following bronchoconstrictor challenge supports a role in airway disease.
Aim: We aimed to determine the effect of short-term TGFα expression on ASM thickening and the development of airway hyperresponsiveness (AHR).
Method: TGFα was conditionally expressed in the airway epithelium of transgenic mice (Clara cell secretory protein-rtTA(+/−)/[tetO](7)-TGFα(+/−)) following 10 d exposure to doxycycline in chow. Egr-1 deficient mice on doxycycline (n = 5) were compared with a control group (n = 4) that were wild type for Egr-1 and did not receive doxycycline. Airway and lung mechanics were assessed by the forced oscillation technique and lungs fixed for subsequent airway morphometry.
Results: ASM thickening was detected in TGFα transgenic Egr-1 deficient mice (P < 0.05) following doxycycline treatment for 10 d. AHR was also demonstrated, defined by an exaggerated increase in Newtonian resistance after methacholine challenge (P < 0.05) compared with controls. In comparison, there was no effect on lung elastance or tissue damping before or after methacholine.
Conclusion: Doxycycline induced-TGFα expression in Egr-1 deficient mice, after 10 d, produces ASM remodelling and AHR with no change in parenchymal mechanics. Short-term TGFα expression in airway epithelial cells promotes features characteristic of asthma.
|Item Type:||Conference Extract|
|Keywords:||asthma, lung function|
|Research Division:||Biomedical and Clinical Sciences|
|Research Group:||Cardiovascular medicine and haematology|
|Research Field:||Respiratory diseases|
|Objective Group:||Clinical health|
|Objective Field:||Clinical health not elsewhere classified|
|UTAS Author:||Zosky, GR (Professor Graeme Zosky)|
|Funding Support:||National Health and Medical Research Council (1042235)|
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