Plasminogen activator inhibitor-1 is an immediate early response gene in regenerating rat liver

Plasminogen activator inhibitor-1 (PAI-1), a M(r) 50,000 serine protease inhibitor, is the major physiological inhibitor of plasminogen activation. Quiescent rat hepatocytes do not express the PAI-1 gene in vivo; however, PAI-1 is synthesized both by primary cultures of rat hepatocytes and by hepato...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1994-03, Vol.54 (5), p.1337-1343
Main Authors: THORNTON, A. J, BRUZDZINSKI, C. J, RAPER, S. E, GELEHRTER, T. D
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Blotting, Northern
Cell cycle, cell proliferation
Cell Division - physiology
Cell physiology
Fundamental and applied biological sciences. Psychology
Gene Expression - genetics
Genes, Immediate-Early - physiology
Hepatectomy
Immunohistochemistry
In Situ Hybridization
Liver - cytology
Liver - physiology
Liver - surgery
Liver Regeneration - genetics
Male
Molecular and cellular biology
Plasminogen Activator Inhibitor 1 - analysis
Plasminogen Activator Inhibitor 1 - genetics
Rats
Rats, Inbred F344
Receptors, Cell Surface - genetics
Receptors, Urokinase Plasminogen Activator
RNA, Messenger - analysis
RNA, Messenger - genetics
Time Factors
Tissue Plasminogen Activator - genetics
Transcription, Genetic - genetics
Urokinase-Type Plasminogen Activator - genetics
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Summary:Plasminogen activator inhibitor-1 (PAI-1), a M(r) 50,000 serine protease inhibitor, is the major physiological inhibitor of plasminogen activation. Quiescent rat hepatocytes do not express the PAI-1 gene in vivo; however, PAI-1 is synthesized both by primary cultures of rat hepatocytes and by hepatoma cells in vitro. Furthermore, PAI-1 is expressed by fibroblastic cells in vitro, in response to mitogen stimulation, suggesting a possible connection between hepatocyte PAI-1 expression and cell proliferation. To determine whether PAI-1 is an early growth response gene in hepatocytes in vivo, we analyzed its expression in regenerating rat liver. Male rats underwent partial (70%) hepatectomy (PH) or sham operation (SO), and liver samples were analyzed by Northern blot analysis and in situ hybridization. PAI-1 mRNA was not present at time 0 h, nor at any other time in SO rats but was induced rapidly in regenerating livers, peaking at 2 h and declining to negligible levels by 8 h posthepatectomy. This induction was not inhibited by cycloheximide. In situ hybridization analysis localized PAI-1 transcripts to hepatocytes. Immunohistochemical analysis demonstrated PAI-1-specific staining in hepatocytes in the livers of both PH and SO rats, but the temporal and spatial distribution profiles differed between PH and SO rats. Our studies demonstrate that PAI-1 is an immediate early response gene, transiently expressed in regenerating liver, expression of which may be important in hepatocyte growth and proliferation in vivo.
ISSN:0008-5472
1538-7445