Thrombin regulation of tissue-type plasminogen activator synthesis in cultured human fetal lung fibroblasts.
We examined the effects of thrombin on tissue-type plasminogen activator (t-PA) release and t-PA mRNA levels in cultured human fetal lung fibroblast cells, IMR-90. The secretion of t-PA was increased by thrombin in a dose- and time-dependent manner, but it was not affected by inactivated thrombin with diisopropylfluorophosphate (DFP). Both antithrombin III (ATIII) and heparin cofactor II (HCII), plasma inhibitors to thrombin, inhibited thrombin-induced t-PA release. The thrombin-induced t-PA secretion was preceded by an increase of the steady state level of t-PA-specific mRNA in the cells, suggesting that thrombin activates t-PA gene expression. The t-PA mRNA expression induced by thrombin was completely blocked by pretreatment of the cells with an inhibitor of translation, cycloheximide (CHX). These results suggest that the effect of thrombin on t-PA expression is mediated through its proteolytic activity and the biosynthesis of transcription factor(s).
Hayakawa
Y
Y
Department of Clinical Laboratory Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Japan.
Tazawa
S
S
Ishikawa
T
T
Niiya
K
K
Sakuragawa
N
N
D000990:Antithrombin III / Q000494:pharmacology; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D015844:Heparin Cofactor II / Q000494:pharmacology; D006801:Humans; D007531:Isoflurophate / Q000494:pharmacology; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000196:embryology; D011480:Protease Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D013917:Thrombin / Q000187:drug effects / Q000494:pharmacology*; D010959:Tissue Plasminogen Activator / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism
D011480:Protease Inhibitors; D012333:RNA, Messenger; D007531:Isoflurophate; D015844:Heparin Cofactor II; D000990:Antithrombin III; D003513:Cycloheximide; D013917:Thrombin; D010959:Tissue Plasminogen Activator