Gene expression and regulation of plasminogen activator inhibitor type I in hepatic stellate cells of rat liver.
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.[1]References
- Gene expression and regulation of plasminogen activator inhibitor type I in hepatic stellate cells of rat liver. Knittel, T., Fellmer, P., Ramadori, G. Gastroenterology (1996) [Pubmed]
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