ArticleBlood2017
The integrin PSI domain has an endogenous thiol isomerase function and is a novel target for antiplatelet therapy.
Article in Blood, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
33 citing papers in PubMed, 74 citations in OpenAlex.
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- Platelet CLEC-2 activation leads to GPIb⍺ shedding: Implications for doxorubicin chemotherapy and thrombosis.The Journal of biological chemistry · 2026Article
- Structural basis of HPA-1a alloimmunization in FNAIT and allosteric regulation of integrin conformation.Blood · 2026Article
- High-fat diet increases circulating palmitic acid produced by gut Bacteroides thetaiotaomicron to promote thrombosis.Cell reports. Medicine · 2025Article
- Allosteric Disulfide Bridges in Integrins: The Molecular Switches of Redox Regulation of Integrin-Mediated Cell Functions.Antioxidants (Basel, Switzerland) · 2025Review
- Conformational response of αStructure (London, England : 1993) · 2025Article
- The Role of Thrombo-inflammation in Ischemic Stroke: Focus on the Manipulation and Clinical Application.Molecular neurobiology · 2025Review
- Thiol isomerase ERp18 enhances platelet activation and arterial thrombosis.Research and practice in thrombosis and haemostasis · 2025Article
- Platelets welcome a new protein disulfide isomerase family member.Journal of thrombosis and haemostasis : JTH · 2025Article
- An αIIbβ3 monoclonal antibody traps a semiextended conformation and allosterically inhibits large ligand binding.Blood advances · 2024Article
- Salvianolic acid B inhibits thrombosis and directly blocks the thrombin catalytic site.Research and practice in thrombosis and haemostasis · 2024Article
- Why platelet mechanotransduction matters for hemostasis and thrombosis.Journal of thrombosis and haemostasis : JTH · 2023Review
- SARS-CoV-2 RBD and Its Variants Can Induce Platelet Activation and Clearance: Implications for Antibody Therapy and Vaccinations against COVID-19.Research (Washington, D.C.) · 2023Article
- Doxorubicin-Induced Platelet Activation and Clearance Relieved by Salvianolic Acid Compound: Novel Mechanism and Potential Therapy for Chemotherapy-Associated Thrombosis and Thrombocytopenia.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Hypoxia and low temperature upregulate transferrin to induce hypercoagulability at high altitude.Blood · 2022Article
- Novel contact-kinin inhibitor sylvestin targets thromboinflammation and ameliorates ischemic stroke.Cellular and molecular life sciences : CMLS · 2022Article
- Preclinical evaluation of immunotherapeutic regimens for fetal/neonatal alloimmune thrombocytopenia.Blood advances · 2021Article
- Neuronal guidance proteins in cardiovascular inflammation.Basic research in cardiology · 2021Review
- Platelet-Cancer Interplay: Molecular Mechanisms and New Therapeutic Avenues.Frontiers in oncology · 2021Review
Corrections and comments
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Authors and funding
23 authors at 5 institutions in 4 countries.
Funding
Abstract
Integrins are a large family of heterodimeric transmembrane receptors differentially expressed on almost all metazoan cells. Integrin β subunits contain a highly conserved plexin-semaphorin-integrin (PSI) domain. The CXXC motif, the active site of the protein-disulfide-isomerase (PDI) family, is expressed twice in this domain of all integrins across species. However, the role of the PSI domain in integrins and whether it contains thiol-isomerase activity have not been explored. Here, recombinant PSI domains of murine β3, and human β1 and β2 integrins were generated and their PDI-like activity was demonstrated by refolding of reduced/denatured RNase. We identified that both CXXC motifs of β3 integrin PSI domain are required to maintain its optimal PDI-like activity. Cysteine substitutions (C13A and C26A) of the CXXC motifs also significantly decreased the PDI-like activity of full-length human recombinant β3 subunit. We further developed mouse anti-mouse β3 PSI domain monoclonal antibodies (mAbs) that cross-react with human and other species. These mAbs inhibited αIIbβ3 PDI-like activity and its fibrinogen binding. Using single-molecular Biomembrane-Force-Probe assays, we demonstrated that inhibition of αIIbβ3 endogenous PDI-like activity reduced αIIbβ3-fibrinogen interaction, and these anti-PSI mAbs inhibited fibrinogen binding via different levels of both PDI-like activity-dependent and -independent mechanisms. Importantly, these mAbs inhibited murine/human platelet aggregation in vitro and ex vivo, and murine thrombus formation in vivo, without significantly affecting bleeding time or platelet count. Thus, the PSI domain is a potential regulator of integrin activation and a novel target for antithrombotic therapies. These findings may have broad implications for all integrin functions, and cell-cell and cell-matrix interactions.
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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.