Induction of hepatic tissue-type plasminogen activator and type 1 plasminogen activator-inhibitor gene expressions and appearance of their translation products in the bile following acute liver injury in rats

Background/Aims: The plasminogen activator (PA)-plasmin system is primarily involved in fibrinolysis, but is also in the patho/physiological events in which breakdown of extracellular matrices is evoked topically. In this pre sent study, we examined the expression of fibrinolytic factors, tissue-type PA (t-PA) and Type 1 PA inhibitor (PAI-1), in acute liver injury. Methods: Acute liver injury was produced in rats by the intraperitoneal administrat ion of carbon tetrachloride (CCl4). Plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were measured to verify the hepatocellular damage. t-PA and PAI-1 gene expressions were measured by Nor thern blotting, and the cell type(s) expressing these genes was identified by in situ hybridization. t-PA and PAI-1 levels were measured by enzyme-lin ked immunosorbent assay (ELISA). Results: A single intraperitoneal administ ration Of CCl4 caused severe acute parenchymatous liver injury. Both t-PA a nd PAI-1 gene expressions were induced by the acute liver injury, and plasm a t-PA and PAI-I concentrations were also increased. In situ hybridization studies demonstrated that the hepatocytes were the cells expressing t-PA an d PAI-1 genes during the acute liver injury. t-PA was also augmented in the bile, whereas PAI-1 was decreased there. Conclusions: t-PA and PAI-1 gene expressions are induced in the hepatocytes of rats with acute liver injury. These fibrinolytic factors induced by liver injury may play important role s in liver regeneration. (C) 2001 Elsevier Science Ltd. All rights reserved .