ArticleThe Journal of clinical investigation2008
Protein disulfide isomerase acts as an injury response signal that enhances fibrin generation via tissue factor activation.
Article in The Journal of clinical investigation, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 162 papers.
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The trial behind it
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Who cites it
162 citing papers in PubMed, 316 citations in OpenAlex.
- Isoquercetin for thromboinflammation in sickle cell disease: a randomized double-blind placebo-controlled trial.Blood advances · 2024Trial
- Targeting protein disulfide isomerase with the flavonoid isoquercetin to improve hypercoagulability in advanced cancer.JCI insight · 2019Trial
- Protein disulfide isomerase inhibition blocks thrombin generation in humans by interfering with platelet factor V activation.JCI insight · 2017Trial
- Identification of the thiol isomerase-binding peptide, mastoparan, as a novel inhibitor of shear-induced transforming growth factor β1 (TGF-β1) activation.The Journal of biological chemistry · 2013Trial
- Article
- Luminespib and AZ5104 are effective antithrombotic drugs via targeting the platelet Ero1α-PDI pathway.Science advances · 2026Article
- A monoclonal antibody to platelet αIIbβ3 that inhibits protein disulfide isomerase binding and platelet aggregation.Blood advances · 2026Article
- Endoplasmic Reticulum Redoxome: Protein Folding and Beyond.Biochemistry · 2026Review
- Assays of Thiol Isomerase Activity.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Cell-specific exosomes in sepsis-associated ARDS: from immunometabolic reprogramming to precision medicine.Frontiers in immunology · 2026Review
- Galloylated polyphenols represent a new class of antithrombotic agents with broad activity against thiol isomerases.Journal of thrombosis and haemostasis : JTH · 2025Article
- Transmembrane thiol isomerase TMX1 inhibits fibrin formation by down-regulation of platelet phosphatidylserine exposure.Cell communication and signaling : CCS · 2025Article
- Low-Molecular-Weight Fucoidan Inhibits Thromboinflammation and Ameliorates Deep Vein Thrombosis via Targeting S100A8/A9.Marine drugs · 2025Article
- Recent advances in vascular thiol isomerases: insights into structures, functions in thrombosis and antithrombotic inhibitor development.Thrombosis journal · 2025Review
- Transmembrane thiol isomerase TMX1 counterbalances the effect of ERp46 to inhibit platelet activation and integrin αIIbβ3 function.Research and practice in thrombosis and haemostasis · 2024Article
- Recent advances in vascular thiol isomerases and redox systems in platelet function and thrombosis.Journal of thrombosis and haemostasis : JTH · 2024Review
- Thioredoxin-related transmembrane protein 1 negatively regulates coagulation and phosphatidylserine exposure.Research and practice in thrombosis and haemostasis · 2024Article
- Article
- Impact of tissue factor expression and administration routes on thrombosis development induced by mesenchymal stem/stromal cell infusions: re-evaluating the dogma.Stem cell research & therapy · 2024Article
- Levels of peripheral blood routine, biochemical and coagulation parameters in patients with hemorrhagic fever with renal syndrome and their relationship with prognosis: an observational cohort study.BMC infectious diseases · 2024Observational
102 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 3 countries.
Funding
Abstract
The activation of initiator protein tissue factor (TF) is likely to be a crucial step in the blood coagulation process, which leads to fibrin formation. The stimuli responsible for inducing TF activation are largely undefined. Here we show that the oxidoreductase protein disulfide isomerase (PDI) directly promotes TF-dependent fibrin production during thrombus formation in vivo. After endothelial denudation of mouse carotid arteries, PDI was released at the injury site from adherent platelets and disrupted vessel wall cells. Inhibition of PDI decreased TF-triggered fibrin formation in different in vivo murine models of thrombus formation, as determined by intravital fluorescence microscopy. PDI infusion increased - and, under conditions of decreased platelet adhesion, PDI inhibition reduced - fibrin generation at the injury site, indicating that PDI can directly initiate blood coagulation. In vitro, human platelet-secreted PDI contributed to the activation of cryptic TF on microvesicles (microparticles). Mass spectrometry analyses indicated that part of the extracellular cysteine 209 of TF was constitutively glutathionylated. Mixed disulfide formation contributed to maintaining TF in a state of low functionality. We propose that reduced PDI activates TF by isomerization of a mixed disulfide and a free thiol to an intramolecular disulfide. Our findings suggest that disulfide isomerases can act as injury response signals that trigger the activation of fibrin formation following vessel injury.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.