Gene expression and regulation of plasminogen activator inhibitor type I in hepatic stellate cells of rat liver

Gastroenterology. 1996 Sep;111(3):745-54. doi: 10.1053/gast.1996.v111.pm8780581.

Abstract

Background & aims: Plasminogen activator inhibitor type 1 (PAI-1) plays a crucial role in the regulation of extracellular matrix-degrading enzymes and in the production of fibrogenic mediators such as transforming growth factor beta through inhibition of plasminogen activation. Because hepatic stellate cells (HSCs), the principal matrix-producing cell of the liver, might also affect extracellular matrix degradation and growth factor activation, the aim of this study was to analyze PAI-1 expression and its regulation in HSCs compared with other liver cells.

Methods: PAI-1 synthesis of liver cells at different time points of primary culture was studied by immunoprecipitation of endogenously labeled proteins followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and by Northern blotting.

Results: Among the various types of liver cells, PAI-1 protein and specific transcripts were present in HSCs and endothelial cells, and no major PAI-1 synthesis was detected in Kupffer cells and hepatocytes. Transforming growth factor beta 1, tissue plasminogen activator, and dexamethasone increased PAI-1 production in HSCs.

Conclusions: Apart from their role as the principal connective tissue-producing cell of the liver, HSCs might regulate extracellular matrix accumulation by modulating the activities of matrix-degrading enzymes and fibrogenic mediators through the production of PAI-1.

MeSH terms

  • Animals
  • Cells, Cultured
  • Dexamethasone / pharmacology
  • Gene Expression Regulation*
  • Gene Expression*
  • Glucocorticoids / pharmacology
  • Liver / cytology
  • Liver / physiology*
  • Plasminogen Activator Inhibitor 1 / genetics*
  • Plasminogen Activator Inhibitor 1 / metabolism
  • Plasminogen Activators / pharmacology
  • Rats
  • Rats, Wistar
  • Time Factors
  • Tissue Plasminogen Activator / pharmacology
  • Transforming Growth Factor beta / pharmacology

Substances

  • Glucocorticoids
  • Plasminogen Activator Inhibitor 1
  • Transforming Growth Factor beta
  • Dexamethasone
  • Plasminogen Activators
  • Tissue Plasminogen Activator