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Thromb Haemost 1996; 75(05): 801-807
DOI: 10.1055/s-0038-1650370
Original Article
Schattauer GmbH Stuttgart

Production of Tissue-Type Plasminogen Activator (t-PA) and Type-1 Plasminogen Activator Inhibitor (PAI-1) in Mildly Cirrhotic Rat Liver

Taiichiro Seki
1   The Department of Agricultural and Biological Chemistry, Nihon University College of Bioresource Science, Tokyo, Japan
3   The Department of Human Genetics, The University of Michigan Medical School, Ann Arbor, USA
,
Hideo Imai
2   The Department of Pharmacology, Taisho Pharmaceutical Co., Ltd. Research Center, Saitama, Japan
,
Shigeyuki Uno
1   The Department of Agricultural and Biological Chemistry, Nihon University College of Bioresource Science, Tokyo, Japan
,
Toyohiko Ariga
1   The Department of Agricultural and Biological Chemistry, Nihon University College of Bioresource Science, Tokyo, Japan
,
Thomas D Gelehrter
3   The Department of Human Genetics, The University of Michigan Medical School, Ann Arbor, USA
› Author Affiliations
Further Information

Publication History

Received 28 August 1995

Accepted after resubmission 08 February 1996

Publication Date:
10 July 2018 (online)

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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.

 

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