Elliot, J and Wang, K and Le Cras, T and Larcombe, A and Zosky, GR and James, A and Noble, P, Transforming growth factor alpha increases extracellular matrix within a transgenic mouse model of airway disease, Respirology, 27 March - 1 April, 2015, Gold Coast, Australia, pp. 96. ISSN 1323-7799 (2015) [Conference Extract]
Increased expression of transforming growth factor alpha (TGF-α) and its receptor, epidermal growth factor receptor, may contribute to the increased thickness of airway smooth muscle (ASM) layer in asthma.
Aim: In a transgenic mouse model of increased TGF-α expression, we have examined the number and size of ASM cells and the volume fraction of extracellular matrix (ECM) within the ASM layer.
Methods: TGF-α was conditionally expressed in the airway epithelium of transgenic mice by exposure to doxycycline in chow (from 0, 10 and 14 days) which induces deficiency in early growth response-1 which upregulates TGF-α induced airway disease. On formalin fixed transverse airway sections, stained with haematoxylin (30 μm), the volume density (NV) of ASM cell nuclei was estimated using an optical disector (◊1000) and the ASM area measured. On contiguous thin (0.5 μm) sections (Massonís trichrome) the volume fraction of ECM (VvECM) was estimated. The mean ASM cell volume (VC = 1/ (NV ◊ VvASM)), the number of ASM cells (NL = NV ◊ ASM area ◊ 1 mm) and volumes of ASM and ECM per mm of airway were calculated.
Conclusion: The volume fraction of ECM in the layer of smooth muscle and the average ASM cell size (hypertrophy) are increased in this mouse model, although considerable variablility exists between animals.
|Item Type:||Conference Extract|
|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)|
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