ArticleMilitary Medical Research2024
Mechanism of lactic acidemia-promoted pulmonary endothelial cells death in sepsis: role for CIRP-ZBP1-PANoptosis pathway.
Article in Military Medical Research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed.
- ZBP1-mediated Treg cell dysfunction exacerbates neuroimmune dysregulation in Alzheimer's disease under metabolic stress.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Lactate metabolism and protein lactylation in programmed cell death: From novel mechanism to therapeutic strategies in human diseases.Clinical and translational medicine · 2026Review
- Innate immune sensors of inflammasomes and PANoptosomes: structural-mechanistic insights and therapeutic implications.Cell research · 2026Review
- Lactylation and regulated cell death: the substrate defines the outcome.Apoptosis : an international journal on programmed cell death · 2026Article
- 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
- CIRP Promotes Redox-Inflammatory Endothelial Injury in High-Fat Diet-Fed ApoEAntioxidants (Basel, Switzerland) · 2026Article
- Crosstalk between lactylation and other post-translational modifications in health and diseases.Molecular biomedicine · 2026Review
- PANoptosis in life and death across cell types: From innate immunity to therapeutic implications.Cell chemical biology · 2026Review
- Protein lactylation in health and diseases: molecular mechanisms, biological significance, and clinical implications.Signal transduction and targeted therapy · 2026Review
- ZBP1-driven pyroptosis-associated alveolar macrophages exacerbate epithelial dysfunction in sepsis.Cell death & disease · 2026Article
- A brain-lung circuit drives LPS-induced lung injury via sympathetic neutrophil axis.Journal of neuroinflammation · 2026Article
- Review
- Defining critical roles for ZBP1 in PANoptosis utilizing a novel genetic tool for disease modeling and therapeutic development.bioRxiv : the preprint server for biology · 2026Article
- PAFAH2 deficiency drives sepsis-induced vascular leakage by promoting ECHS1-mediated suppression of protein crotonylation and mitochondrial dysfunction.Inflammation and regeneration · 2026Article
- Mannose-modified IL-10 mRNA nanoparticle delivery system promotes M2 macrophage polarization and ameliorates early immune dysregulation in sepsis.Drug delivery and translational research · 2026Article
- The role and mechanism of TNFRSF21 in promoting necroptosis of vascular endothelial cells and inducing vascular leakage in sepsis.Journal of molecular medicine (Berlin, Germany) · 2026Article
- Nanotherapeutic Macrophage-Neuro Reprogramming Through Immunometabolic Crosstalk Mitigates Sepsis-Induced Lung Injury and Neurologic Damage.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Lactylation and acetylation: parallel paths, divergent deeds, and research dilemmas.Journal of translational medicine · 2026Review
- Immune molecular mechanisms of PANoptosis in sepsis-induced acute kidney injury.Inflammation and regeneration · 2026Review
19 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors.
Funding
Abstract
backgroundSepsis is often accompanied by lactic acidemia and acute lung injury (ALI). Clinical studies have established that high serum lactate levels are associated with increased mortality rates in septic patients. We further observed a significant correlation between the levels of cold-inducible RNA-binding protein (CIRP) in plasma and bronchoalveolar lavage fluid (BALF), as well as lactate levels, and the severity of post-sepsis ALI. The underlying mechanism, however, remains elusive.
methodsC57BL/6 wild type (WT), Casp8
resultsIn the current study, we demonstrate that lactate, accumulating during sepsis, promotes the lactylation of CIRP in macrophages, leading to the release of CIRP. Once eCIRP is internalized by PVEC through a Toll-like receptor 4 (TLR4)-mediated endocytosis pathway, it competitively binds to ZBP1 and effectively blocks the interaction between ZBP1 and tripartite motif containing 32 (TRIM32), an E3 ubiquitin ligase targeting ZBP1 for proteasomal degradation. This interference mechanism stabilizes ZBP1, thereby enhancing ZBP1-receptor-interacting protein kinase 3 (RIPK3)-dependent PVEC PANoptosis, a form of cell death involving the simultaneous activation of multiple cell death pathways, thereby exacerbating ALI.
conclusionsThese findings unveil a novel pathway by which lactic acidemia promotes macrophage-derived eCIRP release, which, in turn, mediates ZBP1-dependent PVEC PANoptosis in sepsis-induced ALI. This finding offers new insights into the molecular mechanisms driving sepsis-related pulmonary complications and provides potential new therapeutic strategies.
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