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The regulatory role of TGF‐ β in airway remodeling in asthma
Author(s) -
Makinde Toluwalope,
Murphy Richard F,
Agrawal Devendra K
Publication year - 2007
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/sj.icb.7100044
Subject(s) - transforming growth factor beta , microbiology and biotechnology , extracellular matrix , transforming growth factor , biology , tgf beta signaling pathway , transforming growth factor, beta 3 , tgf beta 1 , cancer research , growth factor , receptor , tgf alpha , biochemistry
Both structural and inflammatory cells are capable of secreting transforming growth factor (TGF)‐ β and expressing TGF‐ β receptors. TGF‐ β can induce multiple cellular responses including differentiation, apoptosis, survival and proliferation, and has been implicated in the development of several pathogenic conditions including cancer and asthma. Elevated levels of TGF‐ β have been reported in the asthmatic airway. TGF‐ β binds to its receptor complex and activates multiple pathways involving proteins such as Sma and Mad homologues, phosphatidylinositol‐3 kinase and the mitogen‐activated protein kinases, leading to the transcription of several genes. Cell type, cellular condition, and microenvironment, all play a role in determining which pathway is activated, which, in turn, is an indication of which gene is to be transcribed. TGF‐ β has been shown to induce apoptosis in airway epithelial cells. A possible role for TGF‐ β in the regulation of epithelial cell adhesion properties has also been reported. Enhancement of goblet cell proliferation by TGF‐ β suggests a role in mucus hyper‐secretion. Elevated levels of TGF‐ β correlate with subepithelial fibrosis. TGF‐ β induces proliferation of fibroblast cells and their differentiation into myofibroblasts and extracellular matrix (ECM) protein synthesis during the development of subepithelial fibrosis. TGF‐ β also induces proliferation and survival of and ECM secretion in airway smooth muscle cells (ASMCs), suggesting a possible cause of increased thickness of airway tissues. TGF‐ β also induces the production and release of vascular endothelial cell growth factor and plasminogen activator inhibitor, contributing to the vascular remodeling in the asthmatic airway. Blocking TGF‐ β activity inhibits epithelial shedding, mucus hyper‐secretion, angiogenesis, ASMC hypertrophy and hyperplasia in an asthmatic mouse model. Reduction of TGF‐ β production and control of TGF‐ β effects would be beneficial in the development of therapeutic intervention for airway remodeling in chronic asthma.