ArticleThe Journal of clinical investigation2015
The C-terminal CGHC motif of protein disulfide isomerase supports thrombosis.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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The trial behind it
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Who cites it
73 citing papers in PubMed, 114 citations in OpenAlex.
- Protein disulfide isomerase inhibition blocks thrombin generation in humans by interfering with platelet factor V activation.JCI insight · 2017Trial
- The protein disulfide isomerase P4HB/PDIA1 modulates cellular and misfolded forms of the prion protein.PLoS pathogens · 2026Article
- 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
- Article
- Endoplasmic Reticulum Redoxome: Protein Folding and Beyond.Biochemistry · 2026Review
- Selective inhibition of ERO1α with M6766, a novel small-molecule inhibitor, prevents arterial thrombosis and ischemic stroke in mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Thiol Isomerases: Enzymatic Mechanisms, Models of Oxidation, and Antagonism by Galloylated Polyphenols.Antioxidants (Basel, Switzerland) · 2025Review
- Extracellular PDI in thrombosis and vascular injury.Thrombosis journal · 2025Review
- Galloylated polyphenols represent a new class of antithrombotic agents with broad activity against thiol isomerases.Journal of thrombosis and haemostasis : JTH · 2025Article
- Endoplasmic reticulum protein 29 negatively regulates platelet functions and thrombosis in mice.Thrombosis journal · 2025Article
- Transmembrane thiol isomerase TMX1 inhibits fibrin formation by down-regulation of platelet phosphatidylserine exposure.Cell communication and signaling : CCS · 2025Article
- Protein disulfide isomerase is essential for osteoblast differentiation in mice.Communications biology · 2025Article
- Recent advances in vascular thiol isomerases: insights into structures, functions in thrombosis and antithrombotic inhibitor development.Thrombosis journal · 2025Review
- Differential transport pathways of saturated and unsaturated fatty acid esters in male mouse hepatocytes.Nature communications · 2025Article
- Thiol isomerase ERp18 enhances platelet activation and arterial thrombosis.Research and practice in thrombosis and haemostasis · 2025Article
- A novel role for protein disulfide isomerase ERp18 in venous thrombosis.Thrombosis journal · 2024Article
- Targeting cargo to an unconventional secretory system within megakaryocytes allows the release of transgenic proteins from platelets.Journal of thrombosis and haemostasis : JTH · 2024Article
- An αIIbβ3 monoclonal antibody traps a semiextended conformation and allosterically inhibits large ligand binding.Blood advances · 2024Article
13 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Protein disulfide isomerase (PDI) has two distinct CGHC redox-active sites; however, the contribution of these sites during different physiologic reactions, including thrombosis, is unknown. Here, we evaluated the role of PDI and redox-active sites of PDI in thrombosis by generating mice with blood cells and vessel wall cells lacking PDI (Mx1-Cre Pdifl/fl mice) and transgenic mice harboring PDI that lacks a functional C-terminal CGHC motif [PDI(ss-oo) mice]. Both mouse models showed decreased fibrin deposition and platelet accumulation in laser-induced cremaster arteriole injury, and PDI(ss-oo) mice had attenuated platelet accumulation in FeCl3-induced mesenteric arterial injury. These defects were rescued by infusion of recombinant PDI containing only a functional C-terminal CGHC motif [PDI(oo-ss)]. PDI infusion restored fibrin formation, but not platelet accumulation, in eptifibatide-treated wild-type mice, suggesting a direct role of PDI in coagulation. In vitro aggregation of platelets from PDI(ss-oo) mice and PDI-null platelets was reduced; however, this defect was rescued by recombinant PDI(oo-ss). In human platelets, recombinant PDI(ss-oo) inhibited aggregation, while recombinant PDI(oo-ss) potentiated aggregation. Platelet secretion assays demonstrated that the C-terminal CGHC motif of PDI is important for P-selectin expression and ATP secretion through a non-αIIbβ3 substrate. In summary, our results indicate that the C-terminal CGHC motif of PDI is important for platelet function and coagulation.
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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.