ArticleBlood advances2021
Heme activates platelets and exacerbates rhabdomyolysis-induced acute kidney injury via CLEC-2 and GPVI/FcRγ.
Article in Blood advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Ferroptosis in acute kidney injury following crush syndrome: A novel target for treatment.Journal of advanced research · 2023Pooled it
- Haemolytic injury and cardiovascular disease.Nature reviews. Cardiology · 2026Review
- Review
- Receptor-Dependent and -Independent Effects of Hemin on Platelet Plasma Membrane Disintegration.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Platelet Membrane Receptors and Signalling Pathways.Handbook of experimental pharmacology · 2026Review
- Succinylcholine-induced rhabdomyolysis in a patient withBiomolecules & biomedicine · 2025Article
- HCAR2 is a novel receptor for heme.Blood advances · 2025Article
- The efficiency of blood cell counts and inflammatory indices in prediction of need for acute kidney injury in patients with crush syndrome.BMC nephrology · 2025Article
- Converging Molecular Mechanisms of Nucleated Cell Death Pathways and Procoagulant Platelet Formation.Cells · 2025Review
- Megakaryocytes transfer mitochondria to bone marrow mesenchymal stromal cells to lower platelet activation.The Journal of clinical investigation · 2025Article
- Platelet glycoprotein VI promotes folic acid-induced acute kidney injury through interaction with tubular epithelial cell-derived galectin-3.Cell communication and signaling : CCS · 2025Article
- Hemin-induced platelet activation is regulated by the ACKR3 chemokine surface receptor and has implications for passivation of vulnerable atherosclerotic plaques.The FEBS journal · 2024Article
- Is Hemopexin a Nephrotoxin or a Marker of Kidney Injury in Renal Ischemia-Reperfusion?Biomolecules · 2024Article
- Assessing the Impact of Morphine on Adverse Outcomes in ACS Patients Treated with P2Y12 Inhibitors: Insights from Multiple Real-World Evidence.Drug design, development and therapy · 2024Article
- Farnesoid X receptor prevents neutrophil extracellular traps via reduced sphingosine-1-phosphate in chronic kidney disease.American journal of physiology. Renal physiology · 2023Article
- Article
- Inflammation, coagulation, and cellular injury in heat-induced shock.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Review
- Novel mechanisms of thrombo-inflammation during infection: spotlight on neutrophil extracellular trap-mediated platelet activation.Research and practice in thrombosis and haemostasis · 2023Article
- CLEC-2 Supports Platelet Aggregation in Mouse but not Human Blood at Arterial Shear.Thrombosis and haemostasis · 2022Article
- Article
Corrections and comments
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
There is increasing evidence that platelets participate in multiple pathophysiological processes other than thrombosis and hemostasis, such as immunity, inflammation, embryonic development, and cancer progression. A recent study revealed that heme (hemin)-activated platelets induce macrophage extracellular traps (METs) and exacerbate rhabdomyolysis-induced acute kidney injury (RAKI); however, how hemin activates platelets remains unclear. Here, we report that both C-type lectin-like receptor-2 (CLEC-2) and glycoprotein VI (GPVI) are platelet hemin receptors and are involved in the exacerbation of RAKI. We investigated hemin-induced platelet aggregation in humans and mice, binding of hemin to CLEC-2 and GPVI, the RAKI-associated phenotype in a mouse model, and in vitro MET formation. Using western blotting and surface plasmon resonance, we showed that hemin activates human platelets by stimulating the phosphorylation of SYK and PLCγ2 and directly binding to both CLEC-2 and GPVI. Furthermore, hemin-induced murine platelet aggregation was partially reduced in CLEC-2-depleted and FcRγ-deficient (equivalent to GPVI-deficient) platelets and almost completely inhibited in CLEC-2-depleted FcRγ-deficient (double-knockout) platelets. In addition, hemin-induced murine platelet aggregation was inhibited by the CLEC-2 inhibitor cobalt hematoporphyrin or GPVI antibody (JAQ-1). Renal dysfunction, tubular injury, and MET formation were attenuated in double-knockout RAKI mice. Furthermore, in vitro MET formation assay showed that the downstream signaling pathway of CLEC-2 and GPVI is involved in MET formation. We propose that both CLEC-2 and GPVI in platelets play an important role in RAKI development.
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