ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2010
Inactivation of hepatocyte nuclear factor-4{alpha} mediates alcohol-induced downregulation of intestinal tight junction proteins.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
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Who cites it
34 citing papers in PubMed, 60 citations in OpenAlex.
- 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
- Hepatocyte nuclear factors dynamically regulate triglyceride metabolic reprogramming in metabolic dysfunction-associated steatotic liver disease: Mechanisms and implications.World journal of hepatology · 2025Review
- Mendelian Randomization Analysis Reveals Causal Associations Between Beverages and Irritable Bowel Syndrome: Alcohol, but Not Others.Food science & nutrition · 2025Article
- Immunology and treatments of fatty liver disease.Archives of toxicology · 2025Review
- HNF4α in Hepatocyte Health and Disease.Seminars in liver disease · 2023Review
- The Influence of Alcohol Consumption on Intestinal Nutrient Absorption: A Comprehensive Review.Nutrients · 2023Review
- Article
- Progressive loss of hepatocyte nuclear factor 4 alpha activity in chronic liver diseases in humans.Hepatology (Baltimore, Md.) · 2022Article
- The amelioration of alcohol-induced liver and intestinal barrier injury byBioengineered · 2022Article
- Ethanol: striking the cardiovascular system by harming the gut microbiota.American journal of physiology. Heart and circulatory physiology · 2021Review
- Translational Approaches with Antioxidant Phytochemicals against Alcohol-Mediated Oxidative Stress, Gut Dysbiosis, Intestinal Barrier Dysfunction, and Fatty Liver Disease.Antioxidants (Basel, Switzerland) · 2021Review
- Article
- Study on the synergistic protective effect ofFood science & nutrition · 2019Article
- Inflammatory response under zinc deficiency is exacerbated by dysfunction of the T helper type 2 lymphocyte-M2 macrophage pathway.Immunology · 2019Article
- Article
- Targeting the gut barrier for the treatment of alcoholic liver disease.Liver research (Beijing, China) · 2017Article
- Role of Zinc in the Development/Progression of Alcoholic Liver Disease.Current treatment options in gastroenterology · 2017Review
- Article
- Alcoholic Liver Disease: Update on the Role of Dietary Fat.Biomolecules · 2016Review
- Preventing Gut Leakiness and Endotoxemia Contributes to the Protective Effect of Zinc on Alcohol-Induced Steatohepatitis in Rats.The Journal of nutrition · 2015Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Chronic alcohol exposure has been shown to increase the gut permeability in the distal intestine, in part, through induction of zinc deficiency. The present study evaluated the molecular mechanisms whereby zinc deficiency mediates alcohol-induced intestinal barrier dysfunction. Examination of zinc finger transcription factors in the gastrointestinal tract of mice revealed a prominent distribution of hepatocyte nuclear factor-4alpha (HNF-4alpha). HNF-4alpha exclusively localizes in the epithelial nuclei and exhibited an increased abundance in mRNA and protein levels in the distal intestine. Chronic alcohol exposure to mice repressed the HNF-4alpha gene expression in the ileum and reduced the protein level and DNA binding activity of HNF-4alpha in all of the intestinal segments with the most remarkable changes in the ileum. Chronic alcohol exposure also decreased the mRNA levels of tight junction proteins, particularly in the ileum. Caco-2 cell culture studies were conducted to determine the role of HNF-4alpha in regulation of the epithelial tight junction and barrier function. Knockdown of HNF-4alpha in Caco-2 cells decreased the mRNA and protein levels of tight junction proteins in association with disruption of the epithelial barrier. Alcohol treatment inactivated HNF-4alpha, which was prevented by N-acetyl-cysteine or zinc. The link between zinc and HNF-4alpha function was confirmed by zinc deprivation, which inhibited HNF-4alpha DNA binding activity. These results indicate that inactivation of HNF-4alpha due to oxidative stress and zinc deficiency is likely a novel mechanism contributing to the deleterious effects of alcohol on the tight junctions and the intestinal barrier function.
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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.