ArticleBlood2015
Platelets and protease-activated receptor-4 contribute to acetaminophen-induced liver injury in mice.
Article in Blood, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
41 citing papers in PubMed, 75 citations in OpenAlex.
- Visualization of intrahepatic activation of coagulation and its contribution to disease progression in mice with acetaminophen-induced acute liver injury.Journal of thrombosis and haemostasis : JTH · 2026Article
- The endothelial growth factor angiopoietin-2 is an accurate prognostic biomarker in patients with acetaminophen-induced acute liver failure.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Platelets mediate neutrophil infiltration and exacerbate liver injury and sinusoidal endothelial cell damage after a severe acetaminophen overdose in mice.Archives of toxicology · 2025Article
- Acute Acetaminophen Hepatotoxicity And Platelet Dysfunction.Journal of medical toxicology : official journal of the American College of Medical Toxicology · 2025Article
- Molecular mechanisms in liver repair and regeneration: from physiology to therapeutics.Signal transduction and targeted therapy · 2025Review
- The C3/C3aR pathway exacerbates acetaminophen-induced mouse liver injury via upregulating podoplanin on the macrophage.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Chitinase 3-like protein 1 deficiency ameliorates drug-induced acute liver injury by inhibition of neutrophil recruitment through lipocalin-2.Frontiers in pharmacology · 2025Article
- Acetaminophen Overdose Reveals PAR4 as a Low-Expressing but Potent Receptor on the Hepatic Endothelium in Mice.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Hidden Power: PAR4's Role in Liver Damage From Acetaminophen Overdose in Mice.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Deletion of TP signaling in macrophages delays liver repair following APAP-induced liver injury by reducing accumulation of reparative macrophage and production of HGF.Inflammation and regeneration · 2024Article
- Acetaminophen Overdose Reveals Protease-Activated Receptor 4 as a Low-Expressing but Potent Receptor on the Hepatic Endothelium.bioRxiv : the preprint server for biology · 2024Article
- Neutrophil-dependent hepatic platelet accumulation and liver injury revealed by acetaminophen dose-response studies.Research and practice in thrombosis and haemostasis · 2024Article
- Assessing Platelet Mitochondrial Dysfunction in a Murine Model of Acute Acetaminophen Toxicity.Journal of medical toxicology : official journal of the American College of Medical Toxicology · 2023Article
- Robust coagulation activation and coagulopathy in mice with experimental acetaminophen-induced liver failure.Journal of thrombosis and haemostasis : JTH · 2023Article
- Transcriptional profiling of drug-induced liver injury biomarkers: association of hepatic Srebf1/Pparα signaling and crosstalk of thrombin, alcohol dehydrogenase, MDR and DNA damage regulators.Molecular and cellular biochemistry · 2023Article
- Altered fibrinogen γ-chain cross-linking in mutant fibrinogen-γJournal of thrombosis and haemostasis : JTH · 2023Article
- YKL-40 promotes chemokine expression following drug-induced liver injury via TF-PAR1 pathway in mice.Frontiers in pharmacology · 2023Article
- Article
- Intravital Microscopy to Study Platelet-Leukocyte-Endothelial Interactions in the Mouse Liver.Journal of visualized experiments : JoVE · 2022Article
- The role of platelet mediated thromboinflammation in acute liver injury.Frontiers in immunology · 2022Review
Corrections and comments
- Commented on by
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Acetaminophen (APAP)-induced liver injury in humans is associated with robust coagulation cascade activation and thrombocytopenia. However, it is not known whether coagulation-driven platelet activation participates in APAP hepatotoxicity. Here, we found that APAP overdose in mice caused liver damage accompanied by significant thrombocytopenia and accumulation of platelets in the liver. These changes were attenuated by administration of the direct thrombin inhibitor lepirudin. Platelet depletion with an anti-CD41 antibody also significantly reduced APAP-mediated liver injury and thrombin generation, indicated by the concentration of thrombin-antithrombin (TAT) complexes in plasma. Compared with APAP-treated wild-type mice, biomarkers of hepatocellular and endothelial damage, plasma TAT concentration, and hepatic platelet accumulation were reduced in mice lacking protease-activated receptor (PAR)-4, which mediates thrombin signaling in mouse platelets. However, selective hematopoietic cell PAR-4 deficiency did not affect APAP-induced liver injury or plasma TAT levels. These results suggest that interconnections between coagulation and hepatic platelet accumulation promote APAP-induced liver injury, independent of platelet PAR-4 signaling. Moreover, the results highlight a potential contribution of nonhematopoietic cell PAR-4 signaling to APAP hepatotoxicity.
Indexed as
Identifiers
What OpenQuestion holds
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.