The contribution of transforming growth factor-β and epidermal growth factor signalling to airway remodelling in chronic asthma
Abstract
Asthma is increasing in prevalence in the developing world, affecting ∼10% of the world’s population. It is characterised by chronic lung inflammation and airway remodelling associated with wheezing, shortness of breath, acute bronchial hyperresponsiveness to a variety of innocuous stimuli and a more rapid decline in lung function over time.Airway remodelling, involving proliferation and differentiation of mesenchymal cells, particularly myofibroblasts and smooth muscle cells, is generally refractory to corticosteroids and makes a major contribution to disease chronicity. Transforming growth factor-β is a potent profibrogenic factor whose expression is increased in the asthmatic airways and is a prime candidate for the initiation and persistence of airway remodelling in asthma.This review highlights the role of transforming growth factor-β in the asthmatic lung, incorporating biosynthesis, signalling pathways and functional outcome.In vivo, however, it is the balance between transforming growth factor-β and other growth factors, such as epidermal growth factor, which will determine the extent of fibrosis in the airways.A fuller comprehension of the actions of transforming growth factor-β, and its interaction with other signalling pathways, such as the epidermal growth factor receptor signalling cascade, may enable development of therapies that control airway remodelling where there is an unmet clinical need.
Key Biomarkers
Symptom Clusters
References (3)
- Bronchoalveolar lavage fluid concentrations of transforming growth factor (TGF)‐β1, TGF‐β2, interleukin (IL)‐4 and IL‐13 after segmental allergen challenge and their effects on α‐smooth muscle actin and collagen III synthesis by primary human lung fibroblastsClinical & Experimental Allergy · 2004
- Disruption of transforming growth factor β signaling and profibrotic responses in normal skin fibroblasts by peroxisome proliferator–activated receptor γArthritis & Rheumatism · 2004
- Eosinophils in chronically inflamed human upper airway tissues express transforming growth factor beta 1 gene (TGF beta 1)Journal of Clinical Investigation · 1992
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