The contribution of transforming growth factor-β and epidermal growth factor signalling to airway remodelling in chronic asthma

The Brooke Laboratories, Division of Infection, Inflammation and Repair, F Level South Lab & Path Block (888), Southampton General Hospital, Southampton SO16 6YD, UK.
European Respiratory Journal (Impact Factor: 7.64). 02/2006; 27(1):208-29. DOI: 10.1183/09031936.06.00130004
Source: PubMed

ABSTRACT 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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    • "Phosphorylated Smad2/3 binds to Smad4 and the complex then translocates to the nucleus. The activated Smad 2/3/4 trimer binds to Smad-binding elements in the regulatory regions of junB and c-Jun, and modulates transcription with other coactivators including the cAMP-response element binding protein (CBP)/p300 histone acetyltransferases [33]. "
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    World Allergy Organization Journal 06/2014; 7(1):13. DOI:10.1186/1939-4551-7-13
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    • "It is initiated by extracellular signals, such as connection with extracellular matrix; collagen or hyaluronic acids and by growth factors; TGF-β and EGF. Among those signals, TGF-β is established how it plays important role in airway remodeling and EMT (Phipps et al., 2004; Boxall et al., 2006; Hackett et al., 2009). TGF-β induces the expression of α-smooth muscle actin and vimentin and the downregulation of E-cadherin expression, inducing the dissolution of polarity of the epithelial cell and intercellular adhesion. "
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    Frontiers in Microbiology 09/2013; 4:263. DOI:10.3389/fmicb.2013.00263 · 3.99 Impact Factor
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    • "In this regard, we did not detect hrGFP positivity in any cells outside of the smooth muscle compartments after allergen challenge by fluorescent microscopy (Fig. 2E). Further, we only collected cells with relatively high levels of hrGFP expression (Fig. 1B), thereby avoiding the potential contamination of myofibroblast cells that are known to express low levels of αSMA [12]. "
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    PLoS ONE 09/2013; 8(9):e74469. DOI:10.1371/journal.pone.0074469 · 3.23 Impact Factor
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