Transforming growth factor alpha increases extracellular matrix within a transgenic mouse model of airway disease

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 (Masson’s 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.