Summary
We have studied the production of tissue-type plasminogen activator (t-PA) and type-1
plasminogen activator inhibitor (PAI-1) in liver of normal rats and in rats with mild
cirrhosis induced by carbon tetrachloride inhalation, to demonstrate the production
of these fibrinolytic components and their pathophysiologic role in the liver in vivo.
Immunohistochemical study of paraffin-embedded liver sections and fibrin autography
of frozen sections showed that the normal rat liver produces very little t-PA or PAI-1.
On the contrary, striking t-PA activity and both t-PA and PAI-1 antigens were observed
in the cirrhotic liver. Both t-PA and PAI-1 in plasma were also markedly increased
in the cirrhotic rats. Because the hepatocyte can internalize t-PA or PA/PAI-1 complexes
from circulation, Northern blot analysis of the total liver RNA was performed to demonstrate
the endogenous synthesis of t-PA and PAI-1 in the liver. Although the normal liver
hardly expresses either t-PA or PAI-1 mRNA, striking t-PA and PAI-1 mRNA expression
was observed in the liver of rats with mild cirrhosis.
These data demonstrate that t-PA and PAI-1 production is strongly upregulated in the
liver in rats with mild cirrhosis. These fibrinolytic components, whose production
is closely associated with liver failure, may play important roles in the regulation
of hepatocyte proliferation and liver regeneration in vivo.
