ArticleProceedings of the National Academy of Sciences of the United States of America2024
Claudin-2 upregulation enhances intestinal permeability, immune activation, dysbiosis, and mortality in sepsis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
35 citing papers in PubMed, 46 citations in OpenAlex.
- Trial
- Gut-immune-PVAT axis is involved in ethanol-induced abdominal aortic dysfunction via IL-17RA, TLR4, and FPR1 signaling.Gut microbes · 2026Article
- Unveiling Gut Homeostasis Disruption in Sepsis: Towards an Integrated Mechanistic and Translational Roadmap.Cell proliferation · 2026Review
- Article
- Intestinal epithelial cell-specific deletion of Jak2 disrupts gut homeostasis.Scientific reports · 2026Article
- Contribution of endometrial microbiome to inflammation-mediated infertility in women undergoing ART.Human reproduction (Oxford, England) · 2026Article
- A short antimicrobial peptides family demonstrates efficacy to infection via a multimodal mechanism of action.Antimicrobial agents and chemotherapy · 2026Article
- Tight Junction Defects in Aganglionic and Ganglionic Colon in Children With Hirschsprung Disease.Laboratory investigation; a journal of technical methods and pathology · 2026Article
- Familial Patterns of Oral-Gut Dysbiosis and Systemic Markers in Periodontitis.Journal of clinical periodontology · 2026Article
- Targeting the Gut in Sepsis: Therapeutic Potential of Medical Gases.Biomolecules · 2026Review
- Article
- Gut barrier-microbiota crosstalk in sepsis: from pathogenesis to potential therapies.Frontiers in immunology · 2026Review
- Bile acid dysregulation in sepsis: mechanisms, clinical implications, and future perspectives.Frontiers in cellular and infection microbiology · 2026Review
- Astragaloside IV ameliorates DSS-induced intestinal epithelial barrier dysfunction associated with modulation of tight junction proteins and MLCK/p-MLC and MyD88/TRAF6 signaling pathways.Frontiers in pharmacology · 2026Article
- Intestinal mucosal barrier injury: insights from interdisciplinary perspectives and therapeutic approaches.Frontiers in nutrition · 2026Review
- Gut microbiome in sepsis: from dysbiotic biomarker to precision and palliative decision-making.Frontiers in medicine · 2026Article
- Source-stratified gut-extraintestinal organ crosstalk in sepsis-associated acute gastrointestinal injury and paralytic ileus: the gut as both driver and target.Frontiers in medicine · 2026Review
- Intestinal barrier in chronic gut and liver diseases: Pathogenesis and therapeutic targets.Acta pharmaceutica Sinica. B · 2025Review
- Age- and Sex-dependent Effects of High-fructose, High-fat Diets on Small Bowel Inflammation and Hepatic Steatosis in F344 Rats.Journal of neurogastroenterology and motility · 2025Article
- Dexmedetomidine regulates the SIRT3-mediated JAK2/STAT3 signaling pathway to protect against sepsis-induced intestinal injury.Scientific reports · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
Intestinal epithelial expression of the tight junction protein claudin-2, which forms paracellular cation and water channels, is precisely regulated during development and in disease. Here, we show that small intestinal epithelial claudin-2 expression is selectively upregulated in septic patients. Similar changes occurred in septic mice, where claudin-2 upregulation coincided with increased flux across the paracellular pore pathway. In order to define the significance of these changes, sepsis was induced in claudin-2 knockout (KO) and wild-type (WT) mice. Sepsis-induced increases in pore pathway permeability were prevented by claudin-2 KO. Moreover, claudin-2 deletion reduced interleukin-17 production and T cell activation and limited intestinal damage. These effects were associated with reduced numbers of neutrophils, macrophages, dendritic cells, and bacteria within the peritoneal fluid of septic claudin-2 KO mice. Most strikingly, claudin-2 deletion dramatically enhanced survival in sepsis. Finally, the microbial changes induced by sepsis were less pathogenic in claudin-2 KO mice as survival of healthy WT mice injected with cecal slurry collected from WT mice 24 h after sepsis was far worse than that of healthy WT mice injected with cecal slurry collected from claudin-2 KO mice 24 h after sepsis. Claudin-2 upregulation and increased pore pathway permeability are, therefore, key intermediates that contribute to development of dysbiosis, intestinal damage, inflammation, ineffective pathogen control, and increased mortality in sepsis. The striking impact of claudin-2 deletion on progression of the lethal cascade activated during sepsis suggests that claudin-2 may be an attractive therapeutic target in septic patients.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.