Fibrin(ogen) drives repair after acetaminophen-induced liver injury via leukocyte α_Mβ₂ integrin-dependent upregulation of Mmp12.

ABSTRACT:

Background & aims

Acetaminophen (APAP)-induced liver injury is coupled with activation of the blood coagulation cascade and fibrin(ogen) accumulation within APAP-injured livers of experimental mice. We sought to define the role of fibrin(ogen) deposition in APAP-induced liver injury and repair.

Methods

Wild-type, fibrinogen-deficient mice, mutant mice with fibrin(ogen) incapable of binding leukocyte α_Mβ₂ integrin (Fibγ^390-396A mice) and matrix metalloproteinase 12 (Mmp12)-deficient mice were fasted, injected with 300mg/kg APAP i.p. and evaluated at a range of time-points. Plasma and liver tissue were analyzed. Rescue of Fibγ^390-396A mice was carried out with exogenous Mmp12. To examine the effect of the allosteric leukocyte integri

SUBMITTER: Kopec AK 

PROVIDER: S-EPMC5362307 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature