ArticleCritical care (London, England)2022
Immune effects of PI3K/Akt/HIF-1α-regulated glycolysis in polymorphonuclear neutrophils during sepsis.
Article in Critical care (London, England), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 147 papers.
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Who cites it
147 citing papers in PubMed, 192 citations in OpenAlex.
- Endogenous H₂S promotes HSPA8 sulfhydration to downregulate HIF1α and prevent ferroptosis in septic myocardial injury.Redox report : communications in free radical research · 2026Article
- Exploring the mechanism of polymorphonuclear neutrophils against sepsis based on immune model.Annals of medicine · 2026Review
- Plasma proteomic profiling of septic shock and acute pancreatitis identifies shared signatures and disease-specific pathways.Scientific reports · 2026Article
- Adaptation of OXPHOS biogenesis to cellular requirements.Protein science : a publication of the Protein Society · 2026Review
- FOLR3+neutrophils contribute to sepsis by exacerbating hyper-inflammation.Genes and immunity · 2026Article
- Pulmonary Hypertension Molecular Switch: HIF Signaling Pathway.Pulmonary circulation · 2026Review
- Epigenetics-mediated pathological alterations and their diagnostic and therapeutic potential in sepsis-associated acute kidney injury.Clinical epigenetics · 2026Review
- MicroRNA-200s attenuate demyelination caused by Angiostrongylus cantonensis in a mouse model by targeting phosphatase and tensin homolog.Neural regeneration research · 2026Article
- Upregulation of mScience China. Life sciences · 2026Article
- YTHDF3 Mediates the Occurrence and Development of Breast Cancer by Regulating Glycolysis Through the mTOR-HIF1α-LHDA Axis.Journal of cellular and molecular medicine · 2026Article
- ChIP-seq and RNA-seq Reveal the Involvement of Histone Lactylation Modification in Early Pregnancy with Subclinical Hypothyroidism.Biochemical genetics · 2026Article
- CXCR5Nature communications · 2026Article
- A Review of HIF-1α-Mediated Integration of Metabolic Reprogramming, Mitochondrial Function, and PI3K/Akt-MAPK-Nrf2-NF-κB Signaling.Antioxidants (Basel, Switzerland) · 2026Review
- Reduced glycoprotein hormone β5 links male aging and testosterone decline to increased adiposity.The Journal of clinical investigation · 2026Article
- FABP4 expression in neutrophils as a predictor of sepsis and SI-ARDS based on BALF transcriptome and peripheral blood validation.Chinese medical journal · 2026Article
- Natural products as multi‑target therapies for sepsis‑induced myocardial dysfunction (Review).International journal of molecular medicine · 2026Review
- Machine learning analysis of s-EASIX for predicting 30-day mortality in sepsis patients from MIMIC-IV.Scientific reports · 2026Article
- Establishment and validation of a rat sepsis model aligned with sepsis-3 via Staphylococcus aureus tail vein infection.Applied microbiology and biotechnology · 2026Article
- Lipid metabolism in homeostasis and disease.Signal transduction and targeted therapy · 2026Review
- Wedelolactone, a Novel TLR2 Agonist, Promotes Neutrophil Differentiation and Ameliorates Neutropenia: A Multi-Omics Approach to Unravel the Mechanism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
87 more citing papers are in PubMed but not listed here.
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10 authors at 1 institution in 1 country.
Funding
Abstract
backgroundEffective removal of pathogenic bacteria is key to improving the prognosis of sepsis. Polymorphonuclear neutrophils (PMNs) are the most important components of innate cellular immunity and play vital roles in clearing pathogenic bacteria. However, the metabolic characteristics and immunomodulatory pathways of PMNs during sepsis have not been investigated. In the present study, we explored the immune metabolism characteristics of PMNs and the mechanism by which neutrophilic glycolysis is regulated during sepsis.
methodsMetabolomics analysis was performed on PMNs isolated from 14 septic patients, 26 patients with acute appendicitis, and 19 healthy volunteers. Transcriptome analysis was performed on the PMNs isolated from the healthy volunteers and the patients with sepsis to assess glycolysis and investigate its mechanism. Lipopolysaccharide (LPS) was used to stimulate the neutrophils isolated from the healthy volunteers at different time intervals to build an LPS-tolerant model. Chemotaxis, phagocytosis, lactate production, oxygen consumption rate (OCR), and extracellular acidification rate (ECAR) were evaluated.
resultsTranscriptomics showed significant changes in glycolysis and the mTOR/HIF-1α signaling pathway during sepsis. Metabolomics revealed that the Warburg effect was significantly altered in the patients with sepsis. We discovered that glycolysis regulated PMNs' chemotaxis and phagocytosis functions during sepsis. Lactate dehydrogenase A (LDHA) downregulation was a key factor in the inhibition of glycolysis in PMNs. This study confirmed that the PI3K/Akt-HIF-1α pathway was involved in the LDHA expression level and also influenced PMNs' chemotaxis and phagocytosis functions.
conclusionsThe inhibition of glycolysis contributed to neutrophil immunosuppression during sepsis and might be controlled by PI3K/Akt-HIF-1α pathway-mediated LDHA downregulation. Our study provides a scientific theoretical basis for the management and treatment of patients with sepsis and promotes to identify therapeutic target for the improvement of immune function in sepsis.
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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.