Loss of fibrinogen rescues mice from the pleiotropic effects of plasminogen deficiency.
Plasmin(ogen) is an extracellular serine protease implicated in the activation of latent growth factors and procollagenase, degradation of extracellular matrix components, and fibrin clearance. Plasminogen (Plg) deficiency in mice results in high mortality, wasting, spontaneous gastrointestinal ulceration, rectal prolapse, and severe thrombosis. Furthermore, Plg-deficient mice display delayed wound healing following skin injury, a defect partly related to impaired keratinocyte migration. We generated mice deficient in Plg and fibrinogen (Fib) and show that removal of fibrin(ogen) from the extracellular environment alleviates the diverse spontaneous pathologies previously associated with Plg deficiency and corrects healing times. Mice deficient in Plg and Fib are phenotypically indistinguishable from Fib-deficient mice. These data suggest that the fundamental and possibly only essential physiological role of Plg is fibrinolysis.
Bugge
T H
TH
Division of Developmental Biology, Children's Hospital Research Foundation, Cincinnati, Ohio 45229, USA.
Kombrinck
K W
KW
Flick
M J
MJ
Daugherty
C C
CC
Danton
M J
MJ
Degen
J L
JL
D000347:Afibrinogenemia / Q000235:genetics / Q000503:physiopathology*; D000367:Age Factors; D000818:Animals; D001778:Blood Coagulation Disorders / Q000209:etiology / Q000235:genetics / Q000401:mortality / Q000503:physiopathology*; D002465:Cell Movement; D004064:Digestive System / Q000473:pathology; D004789:Enzyme Activation; D005340:Fibrinogen / Q000235:genetics; D005342:Fibrinolysis; D015603:Keratinocytes / Q000502:physiology; D008099:Liver / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D010958:Plasminogen / Q000172:deficiency* / Q000235:genetics; D012867:Skin / Q000166:cytology; D012879:Skin Physiological Phenomena; D019282:Wasting Syndrome / Q000209:etiology* / Q000401:mortality; D014945:Wound Healing / Q000235:genetics
D005340:Fibrinogen; D010958:Plasminogen