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PMID: 10980108 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

A total fibrinogen deficiency is compatible with the development of pulmonary fibrosis in mice.

The American journal of pathology ·Vol. 157 ·No. 3 ·2000-09-00 ·Pages 703-8

Ploplis VA, Wilberding J, McLennan L, Liang Z, Cornelissen I, DeFord ME, Rosen ED, Castellino FJ

Abstract

In addition to their well-known roles in hemostasis, fibrinogen (Fg) and fibrin (Fn) have been implicated in a number of other physiological and pathophysiological events. One of these involves the fibroproliferative response after acute lung injury, which is the focus of the current study. Mice with a total Fg deficiency (FG(-/-)) were generated by breeding heterozygous (FG(+/-)) pairs, each of which contained an allele with a targeted deletion of its Fg-gamma-chain gene. The resulting FG(-/-) animals did not possess detectable plasma Fg. FG(-/-) mice were then used to assess the roles of Fg and Fn in a bleomycin-induced acute lung injury model. Intratracheal administration of bleomycin in wild-type and FG(-/-) mice resulted in equivalent deposition of interstitial collagen and fibrotic lesions at days 7 and 14 after administration. This indicates that Fg and/or Fn are not essential for the development of bleomycin-induced pulmonary fibrosis.

MeSH Terms
Afibrinogenemia/genetics,metabolism,pathology Animals Bleomycin Collagen/metabolism DNA/analysis Disease Models, Animal Female Fibrinogen/genetics,metabolism Fluorescent Antibody Technique, Indirect Gene Targeting Heterozygote Homozygote Lung/drug effects,metabolism,pathology Male Mice Mice, Knockout Polymerase Chain Reaction Pulmonary Fibrosis/chemically induced,genetics,metabolism,pathology
Chemicals
fibrinopeptides gamma Bleomycin Fibrinogen Collagen DNA
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Ploplis V A
W. M. Keck Center for Transgene Research and the Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, USA.
Wilberding J
McLennan L
Liang Z
Cornelissen I
DeFord M E
Rosen E D
Castellino F J
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Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
0002-9440
DOI
10.1016/S0002-9440(10)64582-8
Published
2000-09-00
Pages
703-8
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC1885710
Subset
IM
Grants
NHLBI NIH HHS · R37 HL013423 · United States
NHLBI NIH HHS · R01 HL013423 · United States
NHLBI NIH HHS · HL63682 · United States
NHLBI NIH HHS · R01 HL063682 · United States
NHLBI NIH HHS · HL13423 · United States
External Links
PubMed source DOI: 10.1016/S0002-9440(10)64582-8 PMC Full Text View journal details
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