ArticleThe Journal of clinical investigation2015
Platelet-derived HMGB1 is a critical mediator of 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 220 papers, 1 of them a synthesis that pooled it.
What it found
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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
220 citing papers in PubMed, 1 synthesis or guideline pooled it, 359 citations in OpenAlex.
- Incidence of thrombosis in patients with hepatocellular carcinoma: systematic review and meta-analysis.Journal of thrombosis and thrombolysis · 2025Pooled it
- Tissue-specific inflammatory responses to systemic LPS in mice with LysM-lineage Hmgb1 deletion.Brain, behavior, & immunity - health · 2026Article
- Activation of Platelet Caspase-1 and P-Selectin Over-Expression in Sickle Cell Disease Patients: An Involvement of NLRP3 Inflammasome?Journal of cellular and molecular medicine · 2026Article
- Thrombolytic resistance: an important factor leading to the failure of intravenous thrombolytic therapy.Journal of neurology · 2026Review
- Thrombocytosis and the generation of platelet-derived microparticles in the pathophysiology of sickle cell disease.British journal of haematology · 2026Review
- Neutrophil extracellular traps induced by activated platelets as a cause of neutrophil-platelet aggregation in β-thalassaemia/haemoglobin E patients.British journal of haematology · 2026Article
- Platelets as localized conduits of TGF-β1 in the tumor microenvironment: implications for cancer progression and therapy.Human cell · 2026Review
- Platelet homeostasis and heterogeneity in inflammation and sepsis: mechanisms, biological effects, and clinical potential.Cell communication and signaling : CCS · 2026Review
- A 'Tangled Web' in the CNS: unraveling neutrophil extracellular traps in neurological disorders.Molecular neurodegeneration · 2026Review
- Chronic Thromboembolic Pulmonary Hypertension as an Inflammation-Angiogenesis Disorder: From Thrombus Persistence to Dual Pulmonary Vasculopathy.Reviews in cardiovascular medicine · 2026Review
- Serum HMGB1 and Alcohol-Related Liver Disease.Journal of clinical medicine · 2026Article
- HMGB1-Platelet Interactions: Mechanisms and Targeted Therapy Strategies.Thrombosis and haemostasis · 2026Review
- No-reflow phenomenon after vessel recanalization in acute ischemic stroke: mechanisms, diagnosis, and treatment directions.Journal of neurology · 2026Review
- NLRP3 inflammasome-mediated platelet hyperreactivity in sickle cell mice is targetable by BTK inhibition.Biochemical and biophysical research communications · 2026Article
- Targeting Neutrophil Extracellular Traps: A New Strategy for the Treatment of Acute Ischemic Stroke Based on Thrombolysis Resistance.Seminars in thrombosis and hemostasis · 2026Review
- Platelets as Central Modulators of Post-Cardiac Arrest Syndrome: Mechanisms and Therapeutic Implications.Biomolecules · 2026Review
- Ferulic acid in combination with ginsenoside Rb1 alleviates myocardial no-reflow by inhibiting platelet HMGB1 release and NET formation.Chinese medicine · 2026Article
- Integrating Preoperative NLR and PLR with Perioperative Clinical Factors: A Nomogram for Predicting Postoperative CRP Elevation After Laparoscopic Hysterectomy.International journal of women's health · 2026Article
- The hidden battlefield: platelet function in the wake of severe trauma.Frontiers in immunology · 2026Review
- Lipopolysaccharide and HMGB1: key regulatory factors in the pathophysiology of sepsis a mechanistic and therapeutic review.Frontiers in immunology · 2026Review
160 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
25 authors at 4 institutions in 4 countries.
Funding
Abstract
Thrombosis and inflammation are intricately linked in several major clinical disorders, including disseminated intravascular coagulation and acute ischemic events. The damage-associated molecular pattern molecule high-mobility group box 1 (HMGB1) is upregulated by activated platelets in multiple inflammatory diseases; however, the contribution of platelet-derived HMGB1 in thrombosis remains unexplored. Here, we generated transgenic mice with platelet-specific ablation of HMGB1 and determined that platelet-derived HMGB1 is a critical mediator of thrombosis. Mice lacking HMGB1 in platelets exhibited increased bleeding times as well as reduced thrombus formation, platelet aggregation, inflammation, and organ damage during experimental trauma/hemorrhagic shock. Platelets were the major source of HMGB1 within thrombi. In trauma patients, HMGB1 expression on the surface of circulating platelets was markedly upregulated. Moreover, evaluation of isolated platelets revealed that HMGB1 is critical for regulating platelet activation, granule secretion, adhesion, and spreading. These effects were mediated via TLR4- and MyD88-dependent recruitment of platelet guanylyl cyclase (GC) toward the plasma membrane, followed by MyD88/GC complex formation and activation of the cGMP-dependent protein kinase I (cGKI). Thus, we establish platelet-derived HMGB1 as an important mediator of thrombosis and identify a HMGB1-driven link between MyD88 and GC/cGKI in platelets. Additionally, these findings suggest a potential therapeutic target for patients sustaining trauma and other inflammatory disorders associated with abnormal 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.