Regulation of tissue-type plasminogen activator (tPA) and type-1 plasminogen activator inhibitor (PAI-1) gene expression in rat hepatocytes in primary culture.
We have performed a comparative study on tPA and PAI-1 mRNA expression in primary cultures of rat hepatocytes and elucidated the possible regulation of these factors by certain hormonal stimulation. The tPA mRNA increased 2- to 4-fold in the presence of cholera toxin (CT), dibutyryl cyclic AMP (dbcAMP), or 3-isobutyl-1-methyl xanthine (IBMX), but slightly decreased in the presence of dexamethasone. The tPA activity was also changed by these agents in a similar fashion. On the contrary, PAI-1 mRNA decreased with CT, dbcAMP, or IBMX, but increased transiently with dexamethasone. From results obtained with cycloheximide, ongoing protein synthesis was judged to be required for both PAI-1 induction with dexamethasone and PAI-1 suppression with IBMX, but not for the tPA induction with IBMX. Dexamethasone exerted opposite regulatory effects on the tPA mRNA expression depending on its concentration: at 10(-8) to 10(-6) M, it suppressed the expression; whereas at 10(-10) M, it elevated the expression.
Uno
S
S
Department of Nutrition and Physiology, Nihon University College of Bioresource Sciences, 3-34-1 Shimouma, Setagaya-ku, Tokyo 154-8513, Japan.
Nakamura
M
M
Ohomagari
Y
Y
Matsuyama
S
S
Seki
T
T
Ariga
T
T
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D015152:Blotting, Northern; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism / Q000502:physiology; D003907:Dexamethasone / Q000494:pharmacology; D004357:Drug Synergism; D005786:Gene Expression Regulation; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D010959:Tissue Plasminogen Activator / Q000096:biosynthesis* / Q000235:genetics
D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D003994:Bucladesine; D003907:Dexamethasone; D002772:Cholera Toxin; D000242:Cyclic AMP; D010959:Tissue Plasminogen Activator; D015056:1-Methyl-3-isobutylxanthine