ArticleCell death and differentiation2022
Lactate promotes macrophage HMGB1 lactylation, acetylation, and exosomal release in polymicrobial sepsis.
Article in Cell death and differentiation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 548 papers.
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Who cites it
548 citing papers in PubMed, 691 citations in OpenAlex.
- Lactylation: Metabolic epigenetic regulation and cell death mechanisms in myocardial ischemia‒reperfusion injury.Genes & diseases · 2027Review
- Lactylation in influenza a virus infection: Current evidence, knowledge gaps, and future perspectives.Virulence · 2026Review
- Metabolic memory in the kidney: how lactate and lactylation drive the path from acute injury to chronic disease.Renal failure · 2026Review
- Lactylation and exercise: A molecular link to disease alleviation (Review).Molecular medicine reports · 2026Review
- Exercise-induced protein lactylation: From molecular mechanisms to precision health applications.iScience · 2026Review
- Lactate Signal: Modulator of Cellular Energy Production and Anabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- The lactate-lactylation axis in acute kidney injury: mechanisms from metabolic reprogramming to epigenetic regulation and clinical therapeutic prospects.International urology and nephrology · 2026Review
- High mobility group box 1 and its post-translational modifications: Molecular mechanisms underlying neurodegenerative disease pathogenesis.Neural regeneration research · 2026Article
- Lactylation at the metabolic-epigenetic interface in cardiovascular diseases: context-dependent mechanisms and translational roadmap.Journal of advanced research · 2026Review
- Unveiling the "Glycolysis-Lactate-Lactylation" Axis: A Novel Target in Ischemic Cerebrovascular Disease.Neuroscience bulletin · 2026Review
- Lactate metabolism and protein lactylation in programmed cell death: From novel mechanism to therapeutic strategies in human diseases.Clinical and translational medicine · 2026Review
- Unfractionated Heparin and Low-Molecular-Weight Heparin in Sepsis: Anti-Inflammatory and Anticoagulant Effects Versus No Anticoagulation-A Propensity Score-Matched Analysis.Journal of clinical laboratory analysis · 2026Article
- HMGB1 Post-Translational Modifications in Epstein-Barr Virus-Associated Nasopharyngeal Carcinoma: Current Evidence, Emerging Mechanistic Concepts, and Unresolved Questions.International journal of molecular sciences · 2026Review
- Lactylation Remodels Tumorigenesis, Immune Microenvironment, and Therapeutic Response.Current issues in molecular biology · 2026Review
- Exosome-Based Drug Delivery Systems in Colorectal Cancer: Current Evidence and Future Perspectives.The AAPS journal · 2026Review
- Article
- DAMPs, PAMPs, and Alarmins: From Mechanism to Therapy.MedComm · 2026Review
- Lactate-dependent regulation of ferroptosis: redox homeostasis, lactylation, and translational perspectives.Apoptosis : an international journal on programmed cell death · 2026Review
- Lactylation: A central metabolic-epigenetic driver of sepsis-associated acute kidney injury.Molecular biology reports · 2026Review
- DDX3x Regulates NINJ1 Transcription via Histone Lactylation in Sepsis Associated-Acute Kidney Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
488 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
High circulating levels of lactate and high mobility group box-1 (HMGB1) are associated with the severity and mortality of sepsis. However, it is unclear whether lactate could promote HMGB1 release during sepsis. The present study demonstrated a novel role of lactate in HMGB1 lactylation and acetylation in macrophages during polymicrobial sepsis. We found that macrophages can uptake extracellular lactate via monocarboxylate transporters (MCTs) to promote HMGB1 lactylation via a p300/CBP-dependent mechanism. We also observed that lactate stimulates HMGB1 acetylation by Hippo/YAP-mediated suppression of deacetylase SIRT1 and β-arrestin2-mediated recruitment of acetylases p300/CBP to the nucleus via G protein-coupled receptor 81 (GPR81). The lactylated/acetylated HMGB1 is released from macrophages via exosome secretion which increases endothelium permeability. In vivo reduction of lactate production and/or inhibition of GPR81-mediated signaling decreases circulating exosomal HMGB1 levels and improves survival outcome in polymicrobial sepsis. Our results provide the basis for targeting lactate/lactate-associated signaling to combat sepsis.
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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.