Tissue factor pathway inhibitor induces expression of JUNB and GADD45B mRNAs.
Tissue factor pathway inhibitor (TFPI) is a Kunitz-type protease inhibitor that regulates tissue factor-triggered blood coagulation. It has previously been reported that TFPI inhibits the proliferation of human umbilical vein endothelial cells (HUVECs), suggesting that TFPI may act as more than just a mediator of coagulation through changes in gene expression. By using DNA-array techniques and Northern blot analysis, we here revealed that TFPI transiently induced the mRNA expression of JUNB and GADD45B. The inducible effects were not observed in TFPIdeltaC (lacking the C-terminal basic region) or antithrombin (heparin-binding anticoagulant protease inhibitor). Moreover, the TFPI-induced expression of GADD45B was blocked by receptor-associated protein, which masks the ligand-binding domain of very low density lipoprotein receptor (VLDL-R). In conclusion, this is the first report to show an effect of TFPI on mRNA expression, and suggests that TFPI modulates cellular functions by inducing JUNB and GADD45B expression through binding to VLDL-R.
Shirotani-Ikejima
Hiroko
H
National Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan.
Kokame
Koichi
K
Hamuro
Tsutomu
T
Bu
Guojun
G
Kato
Hisao
H
Miyata
Toshiyuki
T
D000943:Antigens, Differentiation / Q000096:biosynthesis / Q000235:genetics*; D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D026563:LDL-Receptor Related Protein-Associated Protein / Q000494:pharmacology; D008074:Lipoproteins / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis*; D015854:Up-Regulation; D000097642:GADD45 Proteins
D000943:Antigens, Differentiation; D026563:LDL-Receptor Related Protein-Associated Protein; D008074:Lipoproteins; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; C086470:GADD45B protein, human; D000097642:GADD45 Proteins; C051928:lipoprotein-associated coagulation inhibitor