ArticleJournal of thrombosis and haemostasis : JTH2008
Tissue factor pathway inhibitor-gamma is an active alternatively spliced form of tissue factor pathway inhibitor present in mice but not in humans.
Article in Journal of thrombosis and haemostasis : JTH, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 31 citations in OpenAlex.
- Consistent clinical factor VIII equivalency is unlikely for non-factor therapies in hemophilic mice.Haematologica · 2025Article
- Placental Vascular Defects and Embryonic Lethality Triggered by TFPIα Deficiency in Factor V Leiden Mice.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- TFPIα anticoagulant function is highly dependent on protein S in vivo.Science advances · 2024Article
- Platelet tissue factor pathway inhibitor-α dampens cardiac thrombosis and associated fibrosis in mice.Journal of thrombosis and haemostasis : JTH · 2023Article
- The contribution of TFPIα to the hemostatic response to injury in mice.Journal of thrombosis and haemostasis : JTH · 2021Article
- Intrauterine lethality in Tfpi gene disrupted mice is differentially suppressed during mid- and late-gestation by platelet TFPIα overexpression.Journal of thrombosis and haemostasis : JTH · 2021Article
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- Platelet anticoagulant proteins: Modulators of thrombosis propensity within a procoagulant cell.Journal of thrombosis and haemostasis : JTH · 2020Article
- Defective fibrin deposition and thrombus stability in BambiJournal of thrombosis and haemostasis : JTH · 2019Article
- Tissue factor pathway inhibitor primes monocytes for antiphospholipid antibody-induced thrombosis.Blood · 2019Article
- Maintaining extraembryonic expression allows generation of mice with severe tissue factor pathway inhibitor deficiency.Blood advances · 2019Article
- Re-evaluation of mouse tissue factor pathway inhibitor and comparison of mouse and human tissue factor pathway inhibitor physiology.Journal of thrombosis and haemostasis : JTH · 2018Article
- Tissue Factor Pathway Inhibitor: Multiple Anticoagulant Activities for a Single Protein.Arteriosclerosis, thrombosis, and vascular biology · 2016Review
- New insights into the biology of tissue factor pathway inhibitor.Journal of thrombosis and haemostasis : JTH · 2015Review
- Biology of tissue factor pathway inhibitor.Blood · 2014Review
- Protein S is a cofactor for platelet and endothelial tissue factor pathway inhibitor-α but not for cell surface-associated tissue factor pathway inhibitor.Arteriosclerosis, thrombosis, and vascular biology · 2014Article
- Translation of human tissue factor pathway inhibitor-β mRNA is controlled by alternative splicing within the 5' untranslated region.Arteriosclerosis, thrombosis, and vascular biology · 2014Article
- Cellular expression and biological activities of alternatively spliced forms of tissue factor pathway inhibitor.Current opinion in hematology · 2013Review
- Platelet tissue factor pathway inhibitor modulates intravascular coagulation.Thrombosis research · 2012Review
- Caveolae optimize tissue factor-Factor VIIa inhibitory activity of cell-surface-associated tissue factor pathway inhibitor.The Biochemical journal · 2012Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundTissue factor pathway inhibitor (TFPI) is a potent inhibitor of tissue factor procoagulant activity produced as two alternatively spliced isoforms, TFPIalpha and TFPIbeta, which differ in domain structure and mechanism for cell surface association. 3' Rapid amplification of cDNA ends was used to search for new TFPI isoforms. TFPIgamma, a new alternatively spliced form of TFPI, was identified and characterized.
methodsThe tissue expression, cell surface association and anticoagulant activity of TFPIgamma were characterized and compared to those of TFPIalpha and TFPIbeta through studies of mouse and human tissues and expression of recombinant proteins in Chinese hamster ovary (CHO) cells.
resultsTFPIgamma is produced by alternative splicing using the same 5'-splice donor site as TFPIbeta and a 3'-splice acceptor site 276 nucleotides beyond the stop codon of TFPIbeta in exon 8. The resulting protein has the first two Kunitz domains connected to an 18 amino acid C-terminal region specific to TFPIgamma. TFPIgamma mRNA is differentially produced in mouse tissues but is not encoded within the human TFPI gene. When expressed in CHO cells, TFPIgamma is secreted into conditioned media and effectively inhibits tissue factor procoagulant activity.
conclusionsTFPIgamma is a third alternatively spliced form of TFPI that is widely expressed in mouse tissues but not made by human tissues. It contains the first two Kunitz domains and is a secreted, rather than a cell surface-associated, protein. It is a functional anticoagulant and may partially explain the resistance of mice to coagulopathy in tissue factor-mediated models of disease.
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