肝障害後のマウスから得た分離肝細胞における肝再生過程での線溶系因子の解析

抄録

The liver regeneration after injury is regulated by various growth factors and cytokines. Release of these growth factors is deeply related to degradation of extracellular matrix (ECM). This ECM degradation is regulated by the activation of plasminogen (PIg) and matrix metalloproteinase (MMP) systems. The liver regenerations in knockout mice (KO) for fibrinolytic factors were examined by using CCl₄ injection modeI. The ability of liver regeneration was significantly increased in the α₂-antiplasmin (α₂-AP) KO as compared to the wild-type mice (WT), but was significantly decreased in the PlgKO. The proteolytic activity in liver tissue extract from PlgKO after liver injury was lower than that α₂-APKO and WT. These results suggest that the plasmin/α₂-AP system playes an important role in the hepatic repair. Further, we analyzed the liver regeneration by using the hepatocytes isolated from mouse liver. The proliferation ability of the hepatocytes from mice of 5 days after CCl₄ injection was significantly increased in the α₂-APKO as compared to the WT but was decreased in the PlgKO. The Plg bound to the isolated hepatocytes. The activation of Plg was significantly increased in the presence of mouse hepatocytes. The plasmin inhibition by α₂-AP in the presence of mouse hepatocytes was weaker than that in the absence of mouse hepatocytes. These results indicate that the plasmin/α₂-AP system on the surfaces of mouse hepatocytes plays important roles in liver regeneration. [Jpn J Physiol 55 Suppl:S110 (2005)]