Journal of hepatology · 2004
The regulation of liver regeneration by the plasmin/alpha 2-antiplasmin system.
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Okada Kiyotaka, Ueshima Shigeru, Imano Motohiro, Kataoka Kazuo, Matsuo Osamu
Аннотация
BACKGROUND/AIMS: The regeneration after liver injury is regulated by the release and activation of several growth factors. The role of the plasmin/alpha(2)-antiplasmin (alpha(2)-AP) system in liver regeneration was investigated.
METHODS: CCl(4) was injected intraperitoneally into the mice deficient (-/-) in fibrinolytic factors: alpha(2)-AP-/-, plasminogen (Plg) -/-, and Plg-/-.alpha(2)-AP-/-, and wild-type (WT) mice. The liver tissue was examined for its microscopic appearance, fibrinolytic activity, and fibronectin levels.
RESULTS: In the gene deficient and WT mice, the livers exhibited the same extent of necrosis 2 days after the CCl(4) injection. The livers of the WT mice normalized after 7 days, and the alpha(2)-AP-/- mice normalized after 5 days. In contrast, the livers of the Plg-/- and Plg-/-.alpha(2)-AP-/- mice remained in the damaged state until 14 days after the liver injury. The injection of anti-alpha(2)-AP antibody in the WT mice improved the regeneration after the liver injury, and the injection of tranexamic acid in the alpha(2)-AP-/- mice reduced.
CONCLUSIONS: These results suggest that the plasmin/alpha(2)-AP system played an important role in hepatic repair via clearance from the injury area.
METHODS: CCl(4) was injected intraperitoneally into the mice deficient (-/-) in fibrinolytic factors: alpha(2)-AP-/-, plasminogen (Plg) -/-, and Plg-/-.alpha(2)-AP-/-, and wild-type (WT) mice. The liver tissue was examined for its microscopic appearance, fibrinolytic activity, and fibronectin levels.
RESULTS: In the gene deficient and WT mice, the livers exhibited the same extent of necrosis 2 days after the CCl(4) injection. The livers of the WT mice normalized after 7 days, and the alpha(2)-AP-/- mice normalized after 5 days. In contrast, the livers of the Plg-/- and Plg-/-.alpha(2)-AP-/- mice remained in the damaged state until 14 days after the liver injury. The injection of anti-alpha(2)-AP antibody in the WT mice improved the regeneration after the liver injury, and the injection of tranexamic acid in the alpha(2)-AP-/- mice reduced.
CONCLUSIONS: These results suggest that the plasmin/alpha(2)-AP system played an important role in hepatic repair via clearance from the injury area.
Предметные рубрики MeSH
AnimalsCarbon TetrachlorideCell DivisionChemical and Drug Induced Liver InjuryExtracellular Matrix ProteinsFibrinFibrinolysinFibrinolysisFibronectinsInjectionsLiverLiver DiseasesLiver RegenerationMiceMice, KnockoutNecrosisNeutralization TestsPlasminogen Activator Inhibitor 2Tranexamic Acidalpha-2-Antiplasmin