The interaction between liver regeneration and fibrinolytic enzymes

Abstract

The liver regeneration after injury is regulated by various of growth factors and cytokines. Release and activation of these growth factors are deeply related to degradation of extracellular matrix (ECM). This ECM degradation is regulated by proteolytic system as well as fibrinolytic system. This present study was aimed to confirm the direct interaction between plasminogen (Plg) or urokinase-type Plg activator (u-PA) and hepatocytes. The mouse hepatocytes bound to Plg or u-PA. The activation of Plg was significantly increased in the presence of hepatocytes. The plasmin inhibition by α₂-antiplasmin (α₂-AP) in the presence of hepatocytes was weaker than that in the absence of hepatocytes. The liver regenerations in knockout mice (KO) for fibrinolytic factors were examined by using CCl₄ injection model. The ability of liver regeneration was significantly increased in the α₂-APKO as compared to the wild-type mice (WT) and tissue-type Plg activator (t-PA) KO, but significantly decreased in the PlgKO and slightly decreased in the u-PAKO. The hepatic repairs were markedly delayed in the double deficient mice of t-PA and u-PA as PlgKO mice. On the other hand, 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 fibrinolytic factors play an important role in hepatic repair via proteolysis of matrix elements and clearance of cellular debris from injury area by plasmin produced in the area injured. [J Physiol Sci. 2007;57 Suppl:S60]