title: The regulation of fibrosis in airway remodeling in asthma.
abstract: Fibrosis is one of the key pathological features of airway remodeling in asthma. In the normal airway the amount of collagen and other extracellular matrix components is kept in equilibrium by regulation of synthesis and degradation. In asthma this homeostasis is disrupted due to genetic and environmental factors. In the airways of patients with the disease there is increased extracellular matrix deposition, particularly in the reticular basement membrane region, lamina propria and submucosa. Fibrosis is important as it can occur early in the pathogenesis of asthma, be associated with severity and resistant to therapy. In this review we will discuss current knowledge of relaxin and other key regulators of fibrosis in the airway including TGFβ, Smad2/3 and matrix metalloproteinases. As fibrosis is not directly targeted or effectively treated by current asthma drugs including corticosteroids, characterization of airway fibrosis and how it is regulated will be essential for the development of novel therapies for asthma.
authors.affiliation: Department of Allergy and Immunology, Murdoch Children's Research Institute, The Royal Children's Hospital, Melbourne 3052, Australia.
authors.forename: Simon G
authors.initials: SG
authors.lastname: Royce
authors.forename: Victor
authors.initials: V
authors.lastname: Cheng
authors.forename: Chrishan S
authors.initials: CS
authors.lastname: Samuel
authors.forename: Mimi L K
authors.initials: ML
authors.lastname: Tang
mesh_terms: D056151:Airway Remodeling; D001249:Asthma / Q000378:metabolism* / Q000473:pathology*; D003094:Collagen / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000378:metabolism* / Q000473:pathology*; D012065:Relaxin / Q000378:metabolism; D012137:Respiratory System / Q000378:metabolism / Q000473:pathology; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D061965:Matrix Metalloproteinase Inhibitors; C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; D051899:Smad2 Protein; D051900:Smad3 Protein; D019714:Tissue Inhibitor of Metalloproteinases; D016212:Transforming Growth Factor beta; D012065:Relaxin; D003094:Collagen; D020782:Matrix Metalloproteinases