ArticleThe Journal of clinical investigation2019
Epithelial HIF-1α/claudin-1 axis regulates barrier dysfunction in eosinophilic esophagitis.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 92 citations in OpenAlex.
- The microbiota in eosinophilic esophagitis: A systematic review.Journal of gastroenterology and hepatology · 2022Pooled it
- Understanding the Variability of Peanut-Oral Immunotherapy Responses by Multi-Omics Profiling of Immune Cells.Allergy · 2025Trial
- Vascular Endothelial Barrier in Salivary Glands: From Physiological Regulation to Pathological Impairment of Secretion.International journal of molecular sciences · 2026Review
- Eosinophilic Esophagitis: Mechanisms of Disease and Approach to Treatment.Current allergy and asthma reports · 2026Review
- Emerging Insights into the Inflammatory Phenotypes of Eosinophilic Esophagitis.Journal of inflammation research · 2026Review
- Article
- The central regulator HIF-1α in digestive system pathologies: inflammation and cancer.Frontiers in immunology · 2026Review
- Different Effects of Acute and Chronic Hypoxia on Antiviral Capacity of Pulmonary Vascular Endothelial Cells.Journal of immunology research · 2026Article
- Lifting regenerative barriers promotes epithelial cell fate plasticity supporting lineage conversion.Nature communications · 2025Article
- Novel Antimicrobial Protein Fibroblast Growth Factor 8 Accelerates Skin Wound Healing via Directly Inhibiting Bacteria and Activating Glycolysis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The oesophagus as an immune organ.Nature reviews. Gastroenterology & hepatology · 2025Review
- Lack of Hypoxia Inducible Factor-1α Influences on Macrophages Ability to Deal withJID innovations : skin science from molecules to population health · 2025Article
- Differential T follicular helper cell phenotypes distinguish IgE-mediated milk allergy from eosinophilic esophagitis in children.The Journal of allergy and clinical immunology · 2025Article
- MicroRNAs in Plasma-Derived Extracellular Vesicles as Non-Invasive Biomarkers for Eosinophilic Esophagitis.International journal of molecular sciences · 2025Observational
- Microbiota and gastric cancer: from molecular mechanisms to therapeutic strategies.Frontiers in cellular and infection microbiology · 2025Review
- Association of celiac disease with eosinophilic esophagitis: Nationwide register-based cohort study with sibling analyses.The journal of allergy and clinical immunology. Global · 2024Article
- Lifestyle Changes and Industrialization in the Development of Allergic Diseases.Current allergy and asthma reports · 2024Review
- Development and dysfunction of structural cells in eosinophilic esophagitis.The Journal of allergy and clinical immunology · 2024Review
- Age-Related Differences in the Mouse Corneal Epithelial Transcriptome and Their Impact on Corneal Wound Healing.Investigative ophthalmology & visual science · 2024Article
- Protective effect of zinc gluconate on intestinal mucosal barrier injury in antibiotics and LPS-induced mice.Frontiers in microbiology · 2024Article
Corrections and comments
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Authors and funding
19 authors at 6 institutions in 2 countries.
Funding
Abstract
Epithelial barrier dysfunction is a significant factor in many allergic diseases, including eosinophilic esophagitis (EoE). Infiltrating leukocytes and tissue adaptations increase metabolic demands and decrease oxygen availability at barrier surfaces. Understanding of how these processes impact barrier is limited, particularly in allergy. Here, we identified a regulatory axis whereby the oxygen-sensing transcription factor HIF-1α orchestrated epithelial barrier integrity, selectively controlling tight junction CLDN1 (claudin-1). Prolonged experimental hypoxia or HIF1A knockdown suppressed HIF-1α-dependent claudin-1 expression and epithelial barrier function, as documented in 3D organotypic epithelial cultures. L2-IL5OXA mice with EoE-relevant allergic inflammation displayed localized eosinophil oxygen metabolism, tissue hypoxia, and impaired claudin-1 barrier via repression of HIF-1α/claudin-1 signaling, which was restored by transgenic expression of esophageal epithelial-targeted stabilized HIF-1α. EoE patient biopsy analysis identified a repressed HIF-1α/claudin-1 axis, which was restored via pharmacologic HIF-1α stabilization ex vivo. Collectively, these studies reveal HIF-1α's critical role in maintaining barrier and highlight the HIF-1α/claudin-1 axis as a potential therapeutic target for EoE.
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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.