The contribution of transforming growth factor-beta and epidermal growth factor signalling to airway remodelling in chronic asthma.
Asthma is increasing in prevalence in the developing world, affecting approximately 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-beta 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-beta in the asthmatic lung, incorporating biosynthesis, signalling pathways and functional outcome. In vivo, however, it is the balance between transforming growth factor-beta 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-beta, 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.
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The Brooke Laboratories, Division of Infection, Inflammation and Repair, F Level South Lab & Path Block (888), Southampton General Hospital, Southampton SO16 6YD, UK. cbb@soton.ac.uk
Holgate
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Davies
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D001249:Asthma / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002908:Chronic Disease; D004815:Epidermal Growth Factor / Q000096:biosynthesis* / Q000276:immunology; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005109:Extracellular Matrix / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008854:Microscopy, Electron; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000276:immunology
D016212:Transforming Growth Factor beta; D004815:Epidermal Growth Factor