A total fibrinogen deficiency is compatible with the development of pulmonary fibrosis in mice.
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.
Ploplis
V A
VA
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
J
McLennan
L
L
Liang
Z
Z
Cornelissen
I
I
DeFord
M E
ME
Rosen
E D
ED
Castellino
F J
FJ
D000347:Afibrinogenemia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001761:Bleomycin; D003094:Collagen / Q000378:metabolism; D004247:DNA / Q000032:analysis; D004195:Disease Models, Animal; D005260:Female; D005340:Fibrinogen / Q000235:genetics* / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D018390:Gene Targeting; D006579:Heterozygote; D006720:Homozygote; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016133:Polymerase Chain Reaction; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
C027539:fibrinopeptides gamma; D001761:Bleomycin; D005340:Fibrinogen; D003094:Collagen; D004247:DNA