ArticleCell death & disease2021
Neutrophil extracellular traps impair intestinal barrier functions in sepsis by regulating TLR9-mediated endoplasmic reticulum stress pathway.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
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The trial behind it
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Who cites it
87 citing papers in PubMed, 129 citations in OpenAlex.
- Multicenter randomized trial assessing efficacy and safety of aerosolized dornase Alfa in COVID-19 ARDS.Scientific reports · 2025Trial
- Ethanol, acetaldehyde, lipopolysaccharide, and neutrophil extracellular traps: four-pronged attack on gut epithelial barrier in alcohol use disorder.Anatomical record (Hoboken, N.J. : 2007) · 2026Review
- Unveiling Gut Homeostasis Disruption in Sepsis: Towards an Integrated Mechanistic and Translational Roadmap.Cell proliferation · 2026Review
- The inflammatory-autophagy-NETs axis in renal fibrosis: mechanistic crosstalk and pathological feed-forward amplification loops.Molecular and cellular biochemistry · 2026Review
- A 'Tangled Web' in the CNS: unraveling neutrophil extracellular traps in neurological disorders.Molecular neurodegeneration · 2026Review
- EGCG Alleviates Lipopolysaccharide-Induced Septic Shock by Inhibiting NET-Mediated ROS Production by Regulating CXCL2 Expression.Biochemical genetics · 2026Article
- Article
- Neutrophil extracellular traps and severe mycoplasma pneumonia: A clinical observational study.Medicine · 2026Observational
- Neutrophil heterogeneity in Kawasaki disease and multisystem inflammatory syndrome in children.Pediatric research · 2026Review
- Targeting the intestinal barrier with traditional Chinese medicine for non-alcoholic fatty liver disease: mechanistic insights and therapeutic perspectives.Chinese medicine · 2026Review
- Neutrophil extracellular traps in diabetic wound healing: mechanisms, pathological roles, and therapeutic implications.Burns & trauma · 2026Review
- Neutrophil in sepsis: functional aberration and regulated cell death.Frontiers in immunology · 2026Review
- Epithelial Gab1 Restricts Sepsis-Induced Intestinal Injury by Orchestrating TNF/NF-κB Axis.Mediators of inflammation · 2026Article
- Linking Metabolic and Mitochondrial Stress to Regulated Cell Death and Inflammatory Organ Injury in Sepsis.Journal of inflammation research · 2026Review
- Cell-free DNA in sepsis: from molecular insights to clinical management.Military Medical Research · 2025Review
- Secondary Bile Acids Modified by Odoribacter Splanchnicus Alleviate Colitis by Suppressing Neutrophil Extracellular Trap Formation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Src Reduces Neutrophil Extracellular Traps Generation and Resolves Acute Organ Damage.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Pharmacological reduction of neutrophil infiltration reducesbioRxiv : the preprint server for biology · 2025Article
- Intestinal reengineering: Scientific advances in intestinal transplantation.World journal of gastrointestinal surgery · 2025Review
- The role of four ERS-related key genes in sepsis induced organ dysfunction and the forewarning model construction.BMC medical informatics and decision making · 2025Article
27 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Increased neutrophil extracellular traps (NETs) formation has been found to be associated with intestinal inflammation, and it has been reported that NETs may drive the progression of gut dysregulation in sepsis. However, the biological function and regulation of NETs in sepsis-induced intestinal barrier dysfunction are not yet fully understood. First, we found that both circulating biomarkers of NETs and local NETs infiltration in the intestine were significantly increased and had positive correlations with markers of enterocyte injury in abdominal sepsis patients. Moreover, the levels of local citrullinated histone 3 (Cit H3) expression were associated with the levels of BIP expression. To further confirm the role of NETs in sepsis-induced intestinal injury, we compared peptidylarginine deiminase 4 (PAD4)-deficient mice and wild-type (WT) mice in a lethal septic shock model. In WT mice, the Cit H3-DNA complex was markedly increased, and elevated intestinal inflammation and endoplasmic reticulum (ER) stress activation were also found. Furthermore, PAD4 deficiency alleviated intestinal barrier disruption and decreased ER stress activation. Notably, NETs treatment induced intestinal epithelial monolayer barrier disruption and ER stress activation in a dose-dependent manner in vitro, and ER stress inhibition markedly attenuated intestinal apoptosis and tight junction injury. Finally, TLR9 antagonist administration significantly abrogated NETs-induced intestinal epithelial cell death through ER stress inhibition. Our results indicated that NETs could contribute to sepsis-induced intestinal barrier dysfunction by promoting inflammation and apoptosis. Suppression of the TLR9-ER stress signaling pathway can ameliorate NETs-induced intestinal epithelial cell death.
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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.