ArticleCell biology and toxicology2025
Lactate-induced macrophage HMGB1 lactylation promotes neutrophil extracellular trap formation in sepsis-associated acute kidney injury.
Article in Cell biology and toxicology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it.
- A systematic review of protein post-translational modifications in sepsis.Molecular biology reports · 2025Pooled it
- Metabolic memory in the kidney: how lactate and lactylation drive the path from acute injury to chronic disease.Renal failure · 2026Review
- Lactate in acute kidney injury: pathobiology, risk stratification, and clinical interpretation.Renal failure · 2026Review
- Lactate Signal: Modulator of Cellular Energy Production and Anabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- High mobility group box 1 and its post-translational modifications: Molecular mechanisms underlying neurodegenerative disease pathogenesis.Neural regeneration research · 2026Article
- Review
- Lactylation: A central metabolic-epigenetic driver of sepsis-associated acute kidney injury.Molecular biology reports · 2026Review
- Lactate metabolism and protein lactylation in inflammatory and tumor microenvironments.Molecular biomedicine · 2026Review
- Acute-on-Chronic Liver Failure: An Eroded Cliff Hit by a Storm-A Narrative Review.International journal of molecular sciences · 2026Review
- Lactylation: a novel post-translational modification for cGAS-STING pathway.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- E3 Ligases and Deubiquitinases in Controlling High-Mobility Group Box (HMGB) Protein Functions.International journal of molecular sciences · 2026Review
- Lactylation modification in extracellular vesicles: A key regulator of cellular communication.iScience · 2026Review
- Spatiotemporal heterogeneity of neutrophil extracellular traps in hepatocellular carcinoma microenvironment and targeted therapy progress.Journal of translational medicine · 2026Review
- HMGB1-mediated formation of IL-33-abundant NETs drives lung-to-kidney injury in severe pneumonia-associated acute kidney injury.JCI insight · 2026Article
- Spatiotemporal Control of Intercellular Crosstalk: A New Therapeutic Paradigm for Halting Acute Kidney Injury to Chronic Kidney Disease Transition.Biomolecules · 2026Review
- Pioglitazone Attenuates Sepsis-Associated Acute Kidney Injury by Modulating TLR-4/NF-κB Signaling and Improving Survival and Renal Function.Journal of clinical medicine · 2026Article
- Lactylation as a metabolic-epigenetic switch: Mechanisms and roles in cancer, sepsis, trauma, inflammation, and tissue repair.Biochemistry and biophysics reports · 2026Review
- An Enzyme-Like Catalyzed Nanosheets for Redox Stress Oscillation Therapy Against Bacterial Infections.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Exosome-Mediated Intercellular Communication in the Pathological Processes of Gouty Arthritis and Its Treatment.International journal of molecular sciences · 2026Review
- Interaction networks of macrophage glycolysis and inflammation in sepsis: mechanisms and therapeutic potential.Frontiers in immunology · 2026Review
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNeutrophils play a key role in sepsis-associated acute kidney injury (SAKI), a common and life-threatening complication of organ failure. High mobility group box 1 (HMGB1) modulates inflammatory responses and the formation of neutrophil extracellular traps (NETs). The present work aimed to explore whether HMGB1 lactylation promotes NET formation and exacerbates SAKI.
methodsVenous blood samples were collected from healthy volunteers and SAKI patients. A SAKI mouse model was established using the cecal ligation and puncture method. A coculture system of macrophage-derived exosomes and neutrophils was established. Macrophage-derived exosomes were isolated and identified. ELISAs, immunofluorescence staining, coimmunoprecipitation, and Western blotting were utilized to determine protein levels.
resultsElevated blood lactate levels were associated with increased HMGB1 levels in patients with SAKI. In mouse models, lactate increased HMGB1 expression, promoted NET formation, and exacerbated SAKI. Lactate stimulated M1 macrophages to secrete exosomes, leading to the accumulation and release of HMGB1 in the cytoplasm. Additionally, lactate promoted HMGB1 lactylation in macrophages, triggering the release of mitochondrial DNA from neutrophils and activating the cyclic GMP‒AMP synthase/stimulator of interferon genes pathway.
conclusionThis study revealed that lactate-induced HMGB1 lactylation in macrophages plays a role in promoting NET formation in SAKI through the cGAS/STING pathway. These findings suggest that HMGB1 could be a potential target for therapeutic intervention in SAKI.
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