The regulation of liver regeneration by the plasmin/α2-antiplasmin system

Background/Aims: The regeneration after liver injury is regulated by the release and activation of several growth factors. The role of the plasmin/α2-antiplasmin (α2-AP) system in liver regeneration was investigated. Methods: CCl4 was injected intraperitoneally into the mice deficient (−/−) in fibrinolytic factors: α2-AP−/−, plasminogen (Plg) −/−, and Plg−/−•α2-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 CCl4 injection. The livers of the WT mice normalized after 7 days, and the α2-AP−/− mice normalized after 5 days. In contrast, the livers of the Plg−/− and Plg−/−•α2-AP−/− mice remained in the damaged state until 14 days after the liver injury. The injection of anti-α2-AP antibody in the WT mice improved the regeneration after the liver injury, and the injection of tranexamic acid in the α2-AP−/− mice reduced. Conclusions: These results suggest that the plasmin/α2-AP system played an important role in hepatic repair via clearance from the injury area.