title: A mouse model of chronic idiopathic pulmonary fibrosis.
abstract: Chronic idiopathic pulmonary fibrosis (IPF) is a progressive, fatal, and untreatable disease with unclear etiology. There are few models of this chronic pathology, and although delivery of bleomycin to induce acute lung injury is the most common animal model of pulmonary fibrosis, there is considerable uncertainty about whether this acute injury resolves in those animals that survive. In this report, we have systematically followed groups of mice for up to 6 months following a single insult of bleomycin. We assessed changes in lung function and pathology over this time course, with measurements of the diffusion capacity for carbon monoxide, lung mechanics, quantitative stereology, and collagen. Our results show that, while there is some repair over this extended time course, the injury in the lung never fully resolves. This persistent degree of fibrosis may have similarities to many features of human IPF. Thus, these chronic fibrotic changes in mouse lungs could be a useful model to evaluate potential therapeutic interventions to accelerate repair and possible treat this debilitating disease.
authors.affiliation: Department of Environmental Health Sciences, Program in Respiratory Biology and Lung Diseases, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland21205, USA.
authors.forename: Nathachit
authors.initials: N
authors.lastname: Limjunyawong
authors.affiliation: Department of Environmental Health Sciences, Program in Respiratory Biology and Lung Diseases, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland21205, USA.
authors.forename: Wayne
authors.initials: W
authors.lastname: Mitzner
authors.affiliation: Department of Environmental Health Sciences, Program in Respiratory Biology and Lung Diseases, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland21205, USA ; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland21205, USA.
authors.forename: Maureen R
authors.initials: MR
authors.lastname: Horton
keywords: Bleomycin; chronic idiopathic pulmonary fibrosis; diffusing capacity; idiopathic pulmonary fibrosis; pulmonary function; quantitative histology
references.citation: Methods Cell Biol. 2013;113:257-94
references.pmid: 23317906
references.citation: Am J Respir Cell Mol Biol. 2011 Apr;44(4):556-61
references.pmid: 20581099
references.citation: Curr Opin Pulm Med. 2011 Sep;17(5):355-61
references.pmid: 21832918
references.citation: J Appl Physiol (1985). 2011 May;110(5):1455-9
references.pmid: 21310888
references.citation: Am Rev Respir Dis. 1981 Oct;124(4):428-34
references.pmid: 6170243
references.citation: Am Rev Respir Dis. 1979 Jul;120(1):67-73
references.pmid: 88916
references.citation: Am J Respir Cell Mol Biol. 2005 Jul;33(1):9-13
references.pmid: 15964990
references.citation: J Exp Med. 2010 Mar 15;207(3):535-52
references.pmid: 20176803
references.citation: Int J Biochem Cell Biol. 2008;40(3):362-82
references.pmid: 17936056
references.citation: Am J Respir Crit Care Med. 2006 Apr 1;173(7):769-76
references.pmid: 16415276
references.citation: J Pharmacol Exp Ther. 1987 Dec;243(3):1185-94
references.pmid: 2447265
references.citation: Am J Respir Cell Mol Biol. 2013 Aug;49(2):167-79
references.pmid: 23526222
references.citation: J Appl Physiol (1985). 1992 Jan;72(1):168-78
references.pmid: 1537711
references.citation: J Appl Physiol (1985). 2004 May;96(5):1658-64
references.pmid: 15075308
references.citation: Am J Respir Cell Mol Biol. 2003 Sep;29(3 Pt 1):375-80
references.pmid: 12676806
references.citation: J Appl Physiol (1985). 1995 Aug;79(2):560-6
references.pmid: 7592218
references.citation: Lab Invest. 2012 Jun;92(6):917-25
references.pmid: 22469699
references.citation: Int J Exp Pathol. 2002 Jun;83(3):111-9
references.pmid: 12383190
references.citation: Am J Pathol. 2005 Jun;166(6):1593-606
references.pmid: 15920145
references.citation: Am J Pathol. 2005 Nov;167(5):1267-77
references.pmid: 16251411
references.citation: Am J Physiol Lung Cell Mol Physiol. 2010 Oct;299(4):L442-52
references.pmid: 20562227
references.citation: Am Rev Respir Dis. 1978 Feb;117(2):289-97
references.pmid: 76453
references.citation: Am J Pathol. 1974 Nov;77(2):185-97
references.pmid: 4141224
references.citation: Lab Invest. 1984 May;50(5):487-8
references.pmid: 6201673
references.citation: Proc Natl Acad Sci U S A. 2012 Oct 16;109(42):17105-10
references.pmid: 23027935
references.citation: Mikroskopie. 1970 Jun;26(1):57-60
references.pmid: 5530651
references.citation: Am J Respir Crit Care Med. 2001 Jun;163(7):1648-53
references.pmid: 11401889
references.citation: Am J Physiol Lung Cell Mol Physiol. 2008 Feb;294(2):L152-60
references.pmid: 17993587
references.citation: Am J Respir Crit Care Med. 2010 Feb 15;181(4):394-418
references.pmid: 20130146