Gene expression and regulation of plasminogen activator inhibitor type I in hepatic stellate cells of rat liver.
OBJECTIVE
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.
Knittel
T
T
Department of Internal Medicine, University of Göttingen, Germany.
Fellmer
P
P
Ramadori
G
G
D000818:Animals; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D015870:Gene Expression; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000502:physiology*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics* / Q000378:metabolism; D010960:Plasminogen Activators / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D005938:Glucocorticoids; D017395:Plasminogen Activator Inhibitor 1; D016212:Transforming Growth Factor beta; D003907:Dexamethasone; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator