ArticleNature communications2020
The platelet receptor CLEC-2 blocks neutrophil mediated hepatic recovery in acetaminophen induced acute liver failure.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 79 citations in OpenAlex.
- Beyond Hemostasis: Platelets' Multifaceted Functions in Immune Responses.Life (Basel, Switzerland) · 2026Review
- Receptor homodimerization significantly prolongs the lifetime of ligand-induced cross-linking of CLEC-2 but not GPVI.Blood vessels, thrombosis & hemostasis · 2026Article
- Gallium-Doped MXene Nanozymes Protect Liver Through Multi-Death Pathway Blockade and Hepatocyte Regeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Dynamic regulation and targeted interventions of macrophages in ischemia-reperfusion injury.Journal of advanced research · 2026Review
- Platelet-mediated progression of fatty liver disease in metabolic dysfunction-associated steatohepatitis: a pathophysiological review.Frontiers in medicine · 2026Review
- Does Podoplanin (PDPN) Reflect the Involvement of the Immunological System in Coronary Artery Disease Risk? A Single-Center Prospective Analysis.International journal of molecular sciences · 2025Article
- Mechanistic insights into hepatic cell type-specific contributions to acetaminophen-induced acute liver injury.World journal of gastroenterology · 2025Review
- Platelets mediate neutrophil infiltration and exacerbate liver injury and sinusoidal endothelial cell damage after a severe acetaminophen overdose in mice.Archives of toxicology · 2025Article
- Temporal dichotomy of neutrophil function in acute liver injury and repair.JHEP reports : innovation in hepatology · 2025Article
- Underlying mechanisms and treatment of acetaminophen‑induced liver injury (Review).Molecular medicine reports · 2025Review
- Acute Acetaminophen Hepatotoxicity And Platelet Dysfunction.Journal of medical toxicology : official journal of the American College of Medical Toxicology · 2025Article
- Enzyme-Responsive Nanoparachute for Targeted miRNA Delivery: A Protective Strategy Against Acute Liver and Kidney Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- 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
- Innate immune regulation in inflammation resolution and liver regeneration in drug-induced liver injury.Archives of toxicology · 2025Review
- The multiple mechanisms and modes of cell death after acetaminophen overdose.Exploration of digestive diseases · 2025Article
- The dual role of neutrophils in sepsis-associated liver injury.Frontiers in immunology · 2025Review
- Selective Btk inhibition by PRN1008/PRN473 blocks human CLEC-2, and PRN473 reduces venous thrombosis formation in mice.Blood advances · 2024Article
- 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
- Good Cells Go Bad: Immune Dysregulation in the Transition from Acute Liver Injury to Liver Failure After Acetaminophen Overdose.Drug metabolism and disposition: the biological fate of chemicals · 2024Review
- The thrombopoietin mimetic JNJ-26366821 reduces the late injury and accelerates the onset of liver recovery after acetaminophen-induced liver injury in mice.Archives of toxicology · 2024Article
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
Acetaminophen (APAP) is the main cause of acute liver failure in the West. Specific efficacious therapies for acute liver failure (ALF) are limited and time-dependent. The mechanisms that drive irreversible acute liver failure remain poorly characterized. Here we report that the recently discovered platelet receptor CLEC-2 (C-type lectin-like receptor) perpetuates and worsens liver damage after toxic liver injury. Our data demonstrate that blocking platelet CLEC-2 signalling enhances liver recovery from acute toxic liver injuries (APAP and carbon tetrachloride) by increasing tumour necrosis factor-α (TNF-α) production which then enhances reparative hepatic neutrophil recruitment. We provide data from humans and mice demonstrating that platelet CLEC-2 influences the hepatic sterile inflammatory response and that this can be manipulated for therapeutic benefit in acute liver injury. Since CLEC-2 mediated platelet activation is independent of major haemostatic pathways, blocking this pathway represents a coagulopathy-sparing, specific and novel therapy in acute liver failure.
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