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PMID: 9502424 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Differential expression of extracellular matrix remodeling genes in a murine model of bleomycin-induced pulmonary fibrosis.

The American journal of pathology ·Vol. 152 ·No. 3 ·1998-03-00 ·Pages 821-8

Swiderski RE, Dencoff JE, Floerchinger CS, Shapiro SD, Hunninghake GW

Abstract

Exposure to the chemotherapeutic drug bleomycin leads to pulmonary fibrosis in humans and has been widely used in animal models of the disease. Using C57BL/6 bleomycin-sensitive mice, pulmonary fibrosis was induced by multiple intraperitoneal injections of the drug. An increase in the relative amounts of steady-state alpha1(I) procollagen, alpha1(III) procollagen, and fibronectin mRNA as well as histopathological evidence of fibrosis was observed. The effect of bleomycin on the expression of the enzymes responsible for extracellular matrix degradation, the matrix metalloproteinases (MMPs), and their inhibitors (TIMPs), was selective and showed temporal differences during the development of fibrosis. Of the MMPs tested, bleomycin treatment resulted in the up-regulation of gelatinase A and macrophage metalloelastase gene expression in whole-lung homogenates, whereas gelatinase B, stromelysin-1, and interstitial collagenase gene expression was not significantly changed. Timp2 and Timp3, the murine homologues of the respective TIMP genes, were constitutively expressed, whereas Timp1 was markedly up-regulated during fibrosis. The strong correlation between enhanced extracellular matrix gene expression, differential MMP and TIMP gene expression, and histopathological evidence of fibrosis suggest that dysregulated matrix remodeling is likely to contribute to the pathology of bleomycin-induced pulmonary fibrosis.

MeSH Terms
Animals Bleomycin Disease Models, Animal Extracellular Matrix/enzymology Female Fibronectins/genetics,metabolism Gelatinases/genetics,metabolism Gene Expression Regulation, Enzymologic Immunohistochemistry Lung/enzymology Metalloendopeptidases/genetics,metabolism Mice Mice, Inbred C57BL Procollagen/genetics,metabolism Pulmonary Fibrosis/chemically induced,enzymology,pathology RNA, Messenger/metabolism Specific Pathogen-Free Organisms Tissue Inhibitor of Metalloproteinases/genetics,metabolism Up-Regulation
Chemicals
Fibronectins Procollagen RNA, Messenger Tissue Inhibitor of Metalloproteinases Bleomycin Gelatinases Metalloendopeptidases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Swiderski R E
Division of Pulmonary, Critical Care, and Occupational Medicine, University of Iowa College of Medicine, Iowa City 52242, USA.
Dencoff J E
Floerchinger C S
Shapiro S D
Hunninghake G W
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Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
0002-9440
Published
1998-03-00
Pages
821-8
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC1858388
Subset
IM
Grants
NHLBI NIH HHS · HL 37121 · United States
External Links
PubMed source PMC Full Text View journal details
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