ArticleGut2014
Nrf2 deficiency impairs the barrier function of mouse oesophageal epithelium.
Article in Gut, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
What it found
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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
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 95 citations in OpenAlex.
- Pooled it
- Precision metabolic therapy for propionic acidemia.Biochemical pharmacology · 2026Review
- Cellular and molecular dysregulation of the esophageal epithelium in systemic sclerosis.JCI insight · 2026Article
- Acid bile salt induces esophageal mucosal barrier dysfunction through miR-146a-5p-KYNU pathway in gastroesophageal reflux disease.Esophagus : official journal of the Japan Esophageal Society · 2026Article
- Nrf2 as a Molecular Guardian of Redox Balance and Barrier Integrity in IBD.Antioxidants (Basel, Switzerland) · 2025Review
- Health position paper and redox perspectives - Bench to bedside transition for pharmacological regulation of NRF2 in noncommunicable diseases.Redox biology · 2025Review
- Gastroprotective Effect of Linagliptin on Indomethacin-Induced Gastric Ulceration in Mice: Crosstalk Between Oxidative Stress and Inflammasome Pathways.ACS pharmacology & translational science · 2025Article
- Intestinal Epithelial Tight Junction Barrier Regulation by Novel Pathways.Inflammatory bowel diseases · 2025Review
- Investigating the interplay between mitophagy and diabetic neuropathy: Uncovering the hidden secrets of the disease pathology.Pharmacological research · 2024Review
- Mechanism of Action and Therapeutic Implications of Nrf2/HO-1 in Inflammatory Bowel Disease.Antioxidants (Basel, Switzerland) · 2024Review
- Intrauterine Growth Restriction Affects Colonic Barrier FunctionAntioxidants (Basel, Switzerland) · 2024Article
- Transcriptomic Insights into Hub Genes, Immune Infiltration, and Candidate Drugs in Erosive Esophagitis.Journal of inflammation research · 2024Article
- Maternal Selenium-Enriched Yeast Supplementation in Sows Enhances Offspring Growth and Antioxidant Status through the Nrf2/Keap1 Pathway.Antioxidants (Basel, Switzerland) · 2023Article
- A Review of the Potential of Nuclear Factor [Erythroid-Derived 2]-like 2 Activation in Autoimmune Diseases.Brain sciences · 2023Review
- Dietary Betaine Supplementation Enhances Colonic Barrier Function through the Nrf2/Keap1 and TLR4-NF-κB/MAPK Signaling Pathways and Alters Colonic Microbiota in Bama Mini-Pigs.Antioxidants (Basel, Switzerland) · 2023Article
- Dietary Taurine Improves Growth Performance and Intestine Health via the GSH/GSSG Antioxidant System and Nrf2/ARE Signaling Pathway in Weaned Piglets.Antioxidants (Basel, Switzerland) · 2023Article
- Crosstalk between mitochondrial biogenesis and mitophagy to maintain mitochondrial homeostasis.Journal of biomedical science · 2023Review
- The mitophagy pathway and its implications in human diseases.Signal transduction and targeted therapy · 2023Review
- Alpha-tocopherylquinone differentially modulates claudins to enhance intestinal epithelial tight junction barrier via AhR and Nrf2 pathways.Cell reports · 2023Article
- Tight junctions: from molecules to gastrointestinal diseases.Tissue barriers · 2023Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
objectiveAs a major cellular defence mechanism, the Nrf2/Keap1 pathway regulates expression of genes involved in detoxification and stress response. Here we hypothesise that Nrf2 is involved in oesophageal barrier function and plays a protective role against gastro-oesophageal reflux disease (GERD).
designHuman oesophageal biopsy samples, mouse surgical models and Nrf2(-/-) mice were used to assess the role of the Nrf2/Keap1 pathway in oesophageal barrier function. Trans-epithelial electrical resistance (TEER) was measured with mini-Ussing chambers. HE staining and transmission electron microscopy were used to examine tissue morphology, while gene microarray, immunohistochemistry, western blotting and chromatin immunoprecipitation (ChIP) analysis were used to assess gene expression.
resultsNrf2 was expressed in normal oesophageal epithelium and activated in GERD of both humans and mice. Nrf2 deficiency and gastro-oesophageal reflux in mice, alone or in combination, reduced TEER and increased intercellular space in oesophageal epithelium. Nrf2 target genes and gene sets associated with oxidoreductase activity, mitochondrial biogenesis and energy production were downregulated in the oesophageal epithelium of Nrf2(-/-) mice. Consistent with the antioxidative function of Nrf2, a DNA oxidative damage marker (8OHdG) dramatically increased in oesophageal epithelial cells of Nrf2(-/-) mice compared with those of wild-type mice. Interestingly, ATP biogenesis, Cox IV (a mitochondrial protein) and Claudin 4 (Cldn4) expression were downregulated in the oesophageal epithelium of Nrf2(-/-) mice, suggesting that energy-dependent tight junction integrity was subject to Nrf2 regulation. ChIP analysis confirmed the binding of Nrf2 to Cldn4 promoter.
conclusionsNrf2 deficiency impairs oesophageal barrier function through disrupting energy-dependent tight junction.
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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.