ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2013
Gastroesophageal reflux activates the NF-κB pathway and impairs esophageal barrier function in mice.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 47 citations in OpenAlex.
- Ameliorative Effects of Fermented Gold Kiwi on Reflux Esophagitis in a Rat Model.Preventive nutrition and food science · 2026Article
- Immune functions of the esophagus.The Journal of allergy and clinical immunology · 2026Review
- Multidimensional mechanisms and therapies underlying gastroesophageal reflux disease: focus on immunity, signaling pathways, and the microbiota-gut-brain axis.Frontiers in immunology · 2025Review
- The role of the esophageal and intestinal microbiome in gastroesophageal reflux disease: past, present, and future.Frontiers in immunology · 2025Review
- Linking GERD and the Peptide Bombesin: A New Therapeutic Strategy to Modulate Inflammatory, Oxidative Stress and Clinical Biochemistry Parameters.Antioxidants (Basel, Switzerland) · 2024Article
- NF-κB: A novel therapeutic pathway for gastroesophageal reflux disease?World journal of clinical cases · 2022Review
- Herbal Medicine Hewei Jiangni Decoction Is Noninferior to Oral Omeprazole for the Treatment of Nonerosive Gastroesophageal Reflux Disease: A Randomized, Double-Blind, and Double-Dummy Controlled Trail.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- Protective Mechanisms of Liquid Formulations for Gastro-Oesophageal Reflux Disease in a Human Reconstructed Oesophageal Epithelium Model.Medical devices (Auckland, N.Z.) · 2022Article
- P63 Deficiency and CDX2 Overexpression Lead to Barrett's-Like Metaplasia in Mouse Esophageal Epithelium.Digestive diseases and sciences · 2021Article
- Bile reflux and hypopharyngeal cancer (Review).Oncology reports · 2021Review
- Pathophysiology of reflux oesophagitis: role of Toll-like receptors 2 and 4 and Farnesoid X receptor.Virchows Archiv : an international journal of pathology · 2021Article
- Tojapride Reverses Esophageal Epithelial Inflammatory Responses on Reflux Esophagitis Model Rats.Chinese journal of integrative medicine · 2021Article
- Gene expression profiling of inflammatory cytokines in esophageal biopsies of different phenotypes of gastroesophageal reflux disease: a cross-sectional study.BMC gastroenterology · 2021Article
- Article
- In Vitro Modelling of Barrier Impairment Associated with Gastro-Oesophageal Reflux Disease (GERD).Clinical and experimental gastroenterology · 2021Article
- Thiamine Alleviates High-Concentrate-Diet-Induced Oxidative Stress, Apoptosis, and Protects the Rumen Epithelial Barrier Function in Goats.Frontiers in veterinary science · 2021Article
- Article
- Tojapride prevents CaSR-mediated NLRP3 inflammasome activation in oesophageal epithelium irritated by acidic bile salts.Journal of cellular and molecular medicine · 2020Article
- Role of Kruppel-Like Factor 5 in Deoxycholic Acid-Mediated Intestinal Transdifferentiation of Esophageal Squamous Epithelium.Journal of Cancer · 2019Article
- Destruction of the Dorsal Motor Nucleus of the Vagus Aggravates Inflammation and Injury from Acid-Induced Acute Esophagitis in a Rat Model.Analytical cellular pathology (Amsterdam) · 2019Article
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
The barrier function of the esophageal epithelium is a major defense against gastroesophageal reflux disease. Previous studies have shown that reflux damage is reflected in a decrease in transepithelial electrical resistance associated with tight junction alterations in the esophageal epithelium. To develop novel therapies, it is critical to understand the molecular mechanisms whereby contact with a refluxate impairs esophageal barrier function. In this study, surgical models of duodenal and mixed reflux were developed in mice. Mouse esophageal epithelium was analyzed by gene microarray. Gene set enrichment analysis showed upregulation of inflammation-related gene sets and the NF-κB pathway due to reflux. Significance analysis of microarrays revealed upregulation of NF-κB target genes. Overexpression of NF-κB subunits (p50 and p65) and NF-κB target genes (matrix metalloproteinases-3 and -9, IL-1β, IL-6, and IL-8) confirmed activation of the NF-κB pathway in the esophageal epithelium. In addition, real-time PCR, Western blotting, and immunohistochemical staining also showed downregulation and mislocalization of claudins-1 and -4. In a second animal experiment, treatment with an NF-κB inhibitor, BAY 11-7085 (20 mg·kg⁻¹·day⁻¹ ip for 10 days), counteracted the effects of duodenal and mixed reflux on epithelial resistance and NF-κB-regulated cytokines. We conclude that gastroesophageal reflux activates the NF-κB pathway and impairs esophageal barrier function in mice and that targeting the NF-κB pathway may strengthen esophageal barrier function against reflux.
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