The regulation of liver regeneration by the plasmin/alpha 2-antiplasmin system.
OBJECTIVE
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.
Okada
Kiyotaka
K
Department of Physiology, Kinki University School of Medicine, Ohnohigashi 377-2, Osakasayama, Osaka 589-8511, Japan.
Ueshima
Shigeru
S
Imano
Motohiro
M
Kataoka
Kazuo
K
Matsuo
Osamu
O
D000818:Animals; D002251:Carbon Tetrachloride; D002455:Cell Division; D056486:Chemical and Drug Induced Liver Injury; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005337:Fibrin / Q000378:metabolism; D005341:Fibrinolysin / Q000172:deficiency / Q000276:immunology / Q000378:metabolism*; D005342:Fibrinolysis; D005353:Fibronectins / Q000378:metabolism; D007267:Injections; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000473:pathology / Q000503:physiopathology*; D008115:Liver Regeneration / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D009336:Necrosis; D009500:Neutralization Tests; D017396:Plasminogen Activator Inhibitor 2; D014148:Tranexamic Acid / Q000008:administration & dosage / Q000494:pharmacology; D000979:alpha-2-Antiplasmin / Q000276:immunology / Q000378:metabolism*
D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D017396:Plasminogen Activator Inhibitor 2; D000979:alpha-2-Antiplasmin; C037742:plasmin-plasmin inhibitor complex; D014148:Tranexamic Acid; D005337:Fibrin; D002251:Carbon Tetrachloride; D005341:Fibrinolysin