TGF-β1 causes airway fibrosis and increased collagen I and III mRNA in mice

Nicholas Kenyon, R. W. Ward, G. McGrew, Jerold A Last

Research output: Contribution to journalArticle

131 Citations (Scopus)

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)-β1 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-β1 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 β-aminoproprionitrile (BAPN) was administered to TGF-β 1 treated mice to block airway collagen deposition. Airway hyperresponsiveness was also measured after treatment with TGF-β 1. Results: During the 7 days after administration of TGF-β 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-β1, and significantly increased total collagen was found in the airways 4 weeks after TGF-β 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.

Original languageEnglish (US)
Pages (from-to)772-777
Number of pages6
JournalThorax
Volume58
Issue number9
DOIs
StatePublished - Sep 1 2003

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Transforming Growth Factors
Fibrosis
Collagen
Messenger RNA
Aminopropionitrile
Inbred BALB C Mouse
Airway Remodeling
Protein-Lysine 6-Oxidase
Collagen Type III
Extracellular Matrix Proteins
Hydroxyproline
Collagen Type I
Microscopy
Asthma
Animal Models
Inflammation
Light
Antigens
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

TGF-β1 causes airway fibrosis and increased collagen I and III mRNA in mice. / Kenyon, Nicholas; Ward, R. W.; McGrew, G.; Last, Jerold A.

In: Thorax, Vol. 58, No. 9, 01.09.2003, p. 772-777.

Research output: Contribution to journalArticle

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