ArticleNature communications2014
PKM2 regulates the Warburg effect and promotes HMGB1 release in sepsis.
Article in Nature communications, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 285 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
285 citing papers in PubMed, 1 synthesis or guideline pooled it, 507 citations in OpenAlex.
- Inflammasome Targeted Therapy as Novel Treatment Option for Aortic Aneurysms and Dissections: A Systematic Review of the Preclinical Evidence.Frontiers in cardiovascular medicine · 2021Pooled it
- Research on Sepsis and Metabolic Reprogramming from 1998 to 2025: A Bibliometric and Visualized Analysis.Shock (Augusta, Ga.) · 2026Article
- PKM2: A gatekeeper in macrophage metabolic reprogramming.Journal of pharmaceutical analysis · 2026Review
- LKB1 attenuates the transport activity of GLUT1 by regulating the alternative splicing of PKM1/PKM2 in cervical cancer.Journal of gynecologic oncology · 2026Article
- Macrophage metabolism reprogramming in sepsis: Pathogenesis and therapeutic implications (Review).International journal of molecular medicine · 2026Review
- GATM alleviates sepsis-induced acute kidney injury via PDK4-mediated glycolytic reprogramming in renal tubular epithelial cells.Cellular and molecular life sciences : CMLS · 2026Article
- Bioengineered extracellular vesicles escape lysosomal degradation and deliver Tet-PKM2 for macrophage immunometabolic reprogramming and periodontitis treatment.Bioactive materials · 2026Article
- α-AMA induced liver failure is associated with elevation of HMGB1 lactylation modification in mice.BMC gastroenterology · 2026Article
- NDRG1 aggravates Sepsis-Induced acute lung injury via PKM2-dependent activation of STAT3 and NF-κB signaling.BMC immunology · 2026Article
- Targeting the renin-angiotensin system in sepsis-associated AKI: from pathophysiology to precision medicine.Frontiers in immunology · 2026Review
- Peripheral Blood Mononuclear Cells in Sepsis: Immune Trajectories, Monocyte Dysfunction, and Translational Biomarkers.Journal of inflammation research · 2026Review
- Sarcopenia and sepsis fuel a self-perpetuating cycle of immunometabolism decline.Frontiers in immunology · 2026Review
- Immunometabolic reprogramming in sepsis: mechanisms, clinical endotypes, and therapeutic opportunities.Frontiers in immunology · 2026Review
- The interplay between NLRP3 inflammasome and metabolic signals in gouty arthritis.Frontiers in immunology · 2026Review
- Lactylation modification - a bridge between sepsis and macrophage metabolic reprogramming.Frontiers in immunology · 2026Review
- IL-27 Aggravates Sepsis-Induced ARDS by Driving Macrophage Ferroptosis Through Activation of NCOA4-Mediated Ferritinophagy.Journal of inflammation research · 2026Article
- Article
- Crosstalk between arachidonic acid metabolism and glycolysis drives integrated metabolic-inflammatory reprogramming in macrophages.International journal of biological sciences · 2026Article
- Gambogenic acid ameliorates inflammation by inhibiting HK1-mediated Warburg effect and NLRP3 inflammasome activation in sepsis.Acta pharmaceutica Sinica. B · 2026Article
- Pyruvate kinase M2 in Alzheimer's disease: from dysregulation to therapeutic inhibition.Brain communications · 2026Review
225 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Increasing evidence suggests the important role of metabolic reprogramming in the regulation of the innate inflammatory response, but the underlying mechanism remains unclear. Here we provide evidence to support a novel role for the pyruvate kinase M2 (PKM2)-mediated Warburg effect, namely aerobic glycolysis, in the regulation of high-mobility group box 1 (HMGB1) release. PKM2 interacts with hypoxia-inducible factor 1α (HIF1α) and activates the HIF-1α-dependent transcription of enzymes necessary for aerobic glycolysis in macrophages. Knockdown of PKM2, HIF1α and glycolysis-related genes uniformly decreases lactate production and HMGB1 release. Similarly, a potential PKM2 inhibitor, shikonin, reduces serum lactate and HMGB1 levels, and protects mice from lethal endotoxemia and sepsis. Collectively, these findings shed light on a novel mechanism for metabolic control of inflammation by regulating HMGB1 release and highlight the importance of targeting aerobic glycolysis in the treatment of sepsis and other inflammatory diseases.
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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.