ArticleCommunications biology2024
PKM2-mediated STAT3 phosphorylation promotes acute liver failure via regulating NLRP3-dependent pyroptosis.
Article in Communications biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- T cell-derived CCL5 drives macrophage immunometabolic remodeling in chronic prostatitis via the CCR5-ERK-PKM2/HIF-1α axis.Redox biology · 2026Article
- PKM2: A gatekeeper in macrophage metabolic reprogramming.Journal of pharmaceutical analysis · 2026Review
- Oridonin Ameliorates Concanavalin A-Elicited Hepatitis in Mice: Insight into Suppressing TLR7/PKM2/NLRP3-Driven Inflammation and M1/M2 Polarization.Journal of xenobiotics · 2026Article
- Research Progress on Downstream Mechanisms of Glucose Metabolic Reprogramming and Its Role in the Occurrence and Progression of Type 2 Diabetes Mellitus.Biomedicines · 2026Review
- Lactate-Primed NETosis Modulates Hepatic Regeneration During Acute Liver Failure via the TLR9/KLF15/AJUBA Axis.Cell proliferation · 2026Article
- STAT Signaling in Metabolic Disorders: From Molecular Mechanisms to Therapeutic Implications.Cell biochemistry and biophysics · 2026Review
- Celastrol ameliorates atherosclerosis by inhibiting TLR4/STAT3/NLRP3-mediated macrophage pyroptosis.Chinese medicine · 2026Article
- Dimeric PKM2 in chondrocytes impairs mitochondrial homeostasis in osteoarthritis.Cell death & disease · 2026Article
- ROS-Fueled Allies: STAT3, PKM2, and HIF-1α Influencing Energy Metabolism in Hormone-Independent Cancers.International journal of molecular sciences · 2026Article
- Luteolin alleviates PCOS by inhibiting AR/STAT3/NLRP3-mediated granulosa cell pyroptosis.Journal of ovarian research · 2026Article
- Forsythoside E Alleviates Liver Injury by Targeting PKM2 Tetramerization to Promote Macrophage M2 Polarization.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The SPP1-CD44 Signaling Axis Orchestrates Macrophage Metabolism to Promote Early Inflammation in Acute Kidney Injury.International journal of biological sciences · 2026Article
- Molecular mechanisms and regulation of inflammasome activation and signaling: sensing of pathogens and damage molecular patterns.Cellular & molecular immunology · 2025Review
- Macrophage plasticity and glucose metabolism: the role of immunometabolism in pulmonary arterial hypertension.Clinical science (London, England : 1979) · 2025Review
- Pyruvate Kinase M2 Links Metabolism and Epigenetics: A New Target for Liver Disease Treatment.Biomolecules · 2025Review
- PKM2 orchestrates tumor progression via metabolic reprogramming and MDSCs-mediated immune suppression in the tumor microenvironment.Frontiers in immunology · 2025Review
Corrections and comments
- Erratum issued
Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acute liver failure (ALF) is a life-threatening clinical syndrome characterized by high-grade inflammation and multi-organ failure. Our previous study shows that targeting the M2 isoform of pyruvate kinase (PKM2) to inhibit macrophage inflammation may be a promising strategy for ALF treatment. however, the mechanism by which PKM2 regulates the inflammatory response is unclear. Here we demonstrate that PKM2 contributes to ALF by modulating NLRP3-mediated pyroptosis activation in liver macrophages. The specific knockout of PKM2 in myeloid cells reduces mortality and alleviates hepatic injury in D-galactosamine/LPS-induced ALF mice. Single-cell transcriptome analysis suggests that NLRP3 inflammasome activation of macrophages involves in ALF, knockout of PKM2 in macrophages reduces the expression of NLRP3, and activation of pyroptosis. Pharmacological inhibition of the PKM2 nuclear translocation, but not glycolytic activity, protects mice from ALF. Pharmacological and genetic inhibition of PKM2 attenuates NLRP3-mediated pyroptosis activation and consequently reduces the release of IL-1β and IL-18 by macrophages. Mechanistically, PKM2 translocates into the nucleus and combines with STAT3, enhancing its phosphorylation and recruitment to the NLRP3 promoter region, thereby increasing NLRP3 expression. This work defines PKM2 acts as an important nonmetabolic regulator of NLRP3 that modulates pyroptosis activation in macrophages and guides future therapeutic strategies development for ALF.
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