ArticleCell metabolism2023
Hexokinase 2-mediated gene expression via histone lactylation is required for hepatic stellate cell activation and liver fibrosis.
Article in Cell metabolism, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 261 papers.
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Who cites it
261 citing papers in PubMed, 300 citations in OpenAlex.
- Lactylation: Metabolic epigenetic regulation and cell death mechanisms in myocardial ischemia‒reperfusion injury.Genes & diseases · 2027Review
- Lactate Signal: Modulator of Cellular Energy Production and Anabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Lactate-induced MBD2 K186 lactylation promotes YAP1-dependent myofibroblast-like remodeling of Müller cells in diabetic retinopathy.Molecular biomedicine · 2026Article
- H3K18la in periodontal ligament fibroblasts regulates immune niches and alveolar bone remodeling under mechanical loads.International journal of oral science · 2026Article
- Precision pathophysiology in steatotic liver disease.Clinical and molecular hepatology · 2026Review
- S100 Calcium-Binding Protein 16 (S100A16) Promotes Hepatic Stellate Cell Activation Via Erb-B2 Receptor Tyrosine Kinase 2 (ERBB2)-mediated Glycolysis to Facilitate Liver Fibrosis.Cell biochemistry and function · 2026Article
- H3K18 Lactylation Promotes Cell Proliferation in T-Cell Acute Lymphoblastic Leukemia.Journal of cellular biochemistry · 2026Article
- LncRMRP drives bladder cancer invasion via a lactylation-driven positive feedback circuit.Oncogene · 2026Article
- Lactylation: A central metabolic-epigenetic driver of sepsis-associated acute kidney injury.Molecular biology reports · 2026Review
- Glycolytic enolase 1-induced H4K12 lactylation activates quiescent breast cancer stem-like cells in triple-negative breast cancer.Signal transduction and targeted therapy · 2026Article
- Emerging roles of mitophagy in liver fibrosis: Implications for therapy.Acta pharmacologica Sinica · 2026Review
- Skeletal muscle H3K18 lactylation inhibits hepatic gluconeogenesis through IL-6 mediated interorgan communication.Science advances · 2026Article
- With no lysine kinase 1 in hepatic stellate cells promotes mouse and human liver fibrosis through glycolytic triosephosphate isomerase 1.Hepatology (Baltimore, Md.) · 2026Article
- Lysine l-Lactylation: Bridging Metabolism, Chromatin and Disease.Cell proliferation · 2026Review
- Multi-Omics Analysis Identifies Tryptophan Metabolism and Glycolysis as Potential Pathways Involved in the Protective Effects of Tormentic Acid Against Metabolic Associated Fatty Liver Disease.Pharmacology research & perspectives · 2026Article
- p21-activated kinase 4 drives hepatic stellate cell activation and liver fibrosis through the phosphorylation of YAP at T428.Signal transduction and targeted therapy · 2026Article
- Crosstalk between lactylation and other post-translational modifications in health and diseases.Molecular biomedicine · 2026Review
- Protein lactylation in health and diseases: molecular mechanisms, biological significance, and clinical implications.Signal transduction and targeted therapy · 2026Review
- High-salt diet in macrophage-associated metabolic disorders: Mechanisms and therapeutic implications.Chinese medical journal · 2026Review
- IRF7 links HK1-dependent histone lactylation to fibroblast activation and cardiac fibrosis.EMBO molecular medicine · 2026Article
201 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Lactate was implicated in the activation of hepatic stellate cells (HSCs). However, the mechanism by which lactate exerts its effect remains elusive. Using RNA-seq and CUT&Tag chromatin profiling, we found that induction of hexokinase 2 (HK2) expression in activated HSCs is required for induced gene expression by histone lactylation but not histone acetylation. Inhibiting histone lactylation by Hk2 deletion or pharmacological inhibition of lactate production diminishes HSC activation, whereas exogenous lactate but not acetate supplementation rescues the activation phenotype. Thus, lactate produced by activated HSCs determines the HSC fate via histone lactylation. We found that histone acetylation competes with histone lactylation, which could explain why class I HDAC (histone deacetylase) inhibitors impede HSC activation. Finally, HSC-specific or systemic deletion of HK2 inhibits HSC activation and liver fibrosis in vivo. Therefore, we provide evidence that HK2 may be an effective therapeutic target for liver fibrosis.
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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.