title: TGF-beta1 causes airway fibrosis and increased collagen I and III mRNA in mice.
abstract: BACKGROUND
  Subepithelial collagen and extracellular matrix protein deposition are important pathophysiological components of airway remodelling in chronic asthma. Animal models based on the local reaction to antigens show structural alterations in the airway submucosal region and provide important information regarding disease pathophysiology. We describe a murine model of peribronchial fibrosis using intratracheally instilled transforming growth factor (TGF)-beta(1) in BALB/C mice that facilitates a mechanistic approach to understanding the cellular and molecular pathways leading to airway fibrosis.
  
  
  METHODS
  BALB/C mice were intratracheally instilled with either TGF-beta(1) or buffered saline. Airway fibrosis was assessed by light microscopy, hydroxyproline content, and polymerase chain reaction (PCR) for collagen I and III on microdissected airway samples. The lysyl oxidase inhibitor beta-aminoproprionitrile (BAPN) was administered to TGF-beta(1) treated mice to block airway collagen deposition. Airway hyperresponsiveness was also measured after treatment with TGF-beta(1).
  
  
  RESULTS
  During the 7 days after administration of TGF-beta(1) the mice developed increased subepithelial collagen which could be blocked by BAPN. Increased mRNAs for collagen types I and III were seen in microdissected airways 1 week after TGF-beta(1), and significantly increased total collagen was found in the airways 4 weeks after TGF-beta(1). A detectable increase in airway hyperreactivity occurred.
  
  
  CONCLUSIONS
  This new model should facilitate detailed study of airway remodelling that occurs in the absence of detectable cellular inflammation, and allow examination of the functional consequences of a major structural alteration in the conducting airways uncomplicated by inflammatory cell influx.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of California-Davis, Davis, CA 95616, USA.
authors.forename: N J
authors.initials: NJ
authors.lastname: Kenyon
authors.forename: R W
authors.initials: RW
authors.lastname: Ward
authors.forename: G
authors.initials: G
authors.lastname: McGrew
authors.forename: J A
authors.initials: JA
authors.lastname: Last
mesh_terms: D000629:Aminopropionitrile / Q000009:adverse effects; D000818:Animals; D001980:Bronchi / Q000378:metabolism; D001982:Bronchial Diseases / Q000209:etiology* / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D024042:Collagen Type I / Q000378:metabolism*; D024061:Collagen Type III / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D011658:Pulmonary Fibrosis / Q000209:etiology* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; D012333:RNA, Messenger; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D000629:Aminopropionitrile