ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
Lactylation of Histone H3k18 and Egr1 Promotes Endothelial Glycocalyx Degradation in Sepsis-Induced Acute Lung Injury.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 1 of them a synthesis that pooled it.
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Who cites it
66 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
- Article
- Norepinephrine attenuates acute lung injury by protecting mitochondria via the βRedox biology · 2026Article
- Review
- DDX3x Regulates NINJ1 Transcription via Histone Lactylation in Sepsis Associated-Acute Kidney Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Metabolic Reprogramming in Glioblastoma Stem Cells Promotes Radiation Resistance Through a H3K18la/USP30/MBOAT2 Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The Acute Respiratory Distress Syndrome (ARDS): epidemiology, etiology, molecular mechanisms, diagnosis and therapeutic strategies.Molecular biomedicine · 2026Review
- Novel protein acylations in Alzheimer's disease: Molecular, mechanisms, biological significance, and diagnostic and therapeutic potentials.Journal of advanced research · 2026Review
- Research on Sepsis and Metabolic Reprogramming from 1998 to 2025: A Bibliometric and Visualized Analysis.Shock (Augusta, Ga.) · 2026Article
- The landscape of protein post-translational modifications in the pathogenesis of acute respiratory distress syndrome.Journal of thoracic disease · 2026Review
- Protein lactylation in health and diseases: molecular mechanisms, biological significance, and clinical implications.Signal transduction and targeted therapy · 2026Review
- CRISPR-based epigenetic modulation of endothelial dysfunction in sepsis-induced ARDS: a precision medicine framework.Annals of medicine and surgery (2012) · 2026Article
- Mechanistic Studies of Lactate in Heart Failure: From Metabolic Biomarker to Therapeutic Target.Reviews in cardiovascular medicine · 2026Review
- Epigenetics-mediated pathological alterations and their diagnostic and therapeutic potential in sepsis-associated acute kidney injury.Clinical epigenetics · 2026Review
- DHX9 transcriptional upregulation and lactylation at K1024 fuels a glycolysis-histone lactylation loop in osteosarcoma.Journal of translational medicine · 2026Article
- SYVN1-provoked RASA1 ubiquitination promotes pulmonary inflammation in chronic obstructive pulmonary disease.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Biomimetic flowing vessel-on-a-chip recruiting glycocalyx features for investigating dexmedetomidine function.Materials today. Bio · 2026Article
- Review
- Lactylation: a promising target for musculoskeletal disorders via interactions with chronic inflammation.Journal of advanced research · 2026Review
- Histone Lactylation in Immune Cells and Its Predictive Role in Sepsis Progression: A Prospective Observational Study.Shock (Augusta, Ga.) · 2026Observational
6 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
Circulating lactate is a critical biomarker for sepsis-induced acute lung injury (S-ALI) and is strongly associated with poor prognosis. However, whether elevated lactate directly promotes S-ALI and the specific mechanism involved remain unclear. Here, this work shows that lactate causes pulmonary endothelial glycocalyx degradation and worsens ALI during sepsis. Mechanistically, lactate increases the lactylation of K18 of histone H3, which is enriched at the promoter of EGR1 and promotes its transcription, leading to upregulation of heparanase in pulmonary microvascular endothelial cells. In addition, multiple lactylation sites are identified in EGR1, and lactylation is confirmed to occur mainly at K364. K364 lactylation of EGR1 facilitates its interaction with importin-α, in turn promoting its nuclear localization. Importantly, this work identifies KAT2B as a novel lactyltransferase whose GNAT domain directly mediates the lactylation of EGR1 during S-ALI. In vivo, suppression of lactate production or genetic knockout of EGR1 mitigated glycocalyx degradation and ALI and improved survival outcomes in mice with polymicrobial sepsis. Therefore, this study reveals that the crosstalk between metabolic reprogramming in endothelial cells and epigenetic modifications plays a critical role in the pathological processes of S-ALI.
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Registered trials
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