title: The regulatory role of TGF-beta in airway remodeling in asthma.
abstract: Both structural and inflammatory cells are capable of secreting transforming growth factor (TGF)-beta and expressing TGF-beta receptors. TGF-beta 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-beta have been reported in the asthmatic airway. TGF-beta 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-beta has been shown to induce apoptosis in airway epithelial cells. A possible role for TGF-beta in the regulation of epithelial cell adhesion properties has also been reported. Enhancement of goblet cell proliferation by TGF-beta suggests a role in mucus hyper-secretion. Elevated levels of TGF-beta correlate with subepithelial fibrosis. TGF-beta induces proliferation of fibroblast cells and their differentiation into myofibroblasts and extracellular matrix (ECM) protein synthesis during the development of subepithelial fibrosis. TGF-beta 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-beta 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-beta activity inhibits epithelial shedding, mucus hyper-secretion, angiogenesis, ASMC hypertrophy and hyperplasia in an asthmatic mouse model. Reduction of TGF-beta production and control of TGF-beta effects would be beneficial in the development of therapeutic intervention for airway remodeling in chronic asthma.
authors.affiliation: Department of Biomedical Sciences, Creighton University School of Medicine, Omaha, NE 68178, USA.
authors.forename: Toluwalope
authors.initials: T
authors.lastname: Makinde
authors.forename: Richard F
authors.initials: RF
authors.lastname: Murphy
authors.forename: Devendra K
authors.initials: DK
authors.lastname: Agrawal
mesh_terms: D000818:Animals; D001249:Asthma / Q000378:metabolism*; D006801:Humans; D012137:Respiratory System / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology*; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000737:chemistry / Q000378:metabolism*
chemical_list: D016212:Transforming Growth Factor beta