ArticleGastroenterology2011
The epithelial barrier is maintained by in vivo tight junction expansion during pathologic intestinal epithelial shedding.
Article in Gastroenterology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 159 papers.
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Who cites it
159 citing papers in PubMed, 275 citations in OpenAlex.
- Trial
- Article
- Epithelial cell extrusion underlies starvation-induced cell loss in a sea anemone.Nature communications · 2026Article
- Short-chain fatty acids attenuate sepsis-induced gut dysbiosis and hippocampal neuroinflammation via NLRP6 inflammasome activation in mice.International journal of surgery (London, England) · 2026Article
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- Ubiquitination of TFEB increased intestinal permeability to aggravate metabolic dysfunction-associated steatohepatitis.Hepatology (Baltimore, Md.) · 2025Article
- The epithelial barrier theory proposes a comprehensive explanation for the origins of allergic and other chronic noncommunicable diseases.FEBS letters · 2025Review
- Advances in Understanding Intestinal Homeostasis: Lessons from Inflammatory Bowel Disease and Monogenic Intestinal Disorder Pathogenesis.International journal of molecular sciences · 2025Review
- Antigen Uptake in the Gut: An Underappreciated Piece to the Puzzle?Annual review of immunology · 2025Review
- Dysregulation of γδ intraepithelial lymphocytes precedes Crohn's disease-like ileitis.Science immunology · 2025Article
- Phillyrin ameliorates DSS-induced colitis in mice via modulating the gut microbiota and inhibiting the NF-κB/MLCK pathway.Microbiology spectrum · 2025Article
- Mechanism of cell death and its application in the repair of inflammatory bowel disease by mesenchymal stem cells.Frontiers in immunology · 2025Review
- Intestinal pathology in goats challenged withVeterinary pathology · 2025Article
- Phase-dependent iron depletion differentially regulates the niche of intestinal stem cells in experimental colitis via ERK/STAT3 signaling pathway.Frontiers in immunology · 2025Article
- Intestinal mucosal turnover in germ-free piglets infected with E. coli.Journal of molecular histology · 2024Article
- Underneath the Gut-Brain Axis in IBD-Evidence of the Non-Obvious.International journal of molecular sciences · 2024Review
- Review
- Bifidobacterium bifidum Strain BB1 Inhibits Tumor Necrosis Factor-α-Induced Increase in Intestinal Epithelial Tight Junction Permeability via Toll-Like Receptor-2/Toll-Like Receptor-6 Receptor Complex-Dependent Stimulation of Peroxisome Proliferator-Activated Receptor γ and Suppression of NF-κB p65.The American journal of pathology · 2024Article
- Cystathionine Gamma-Lyase Regulates TNF-α-Mediated Injury Response in Human Colonic Epithelial Cells and Colonoids.Antioxidants (Basel, Switzerland) · 2024Article
- α-Ketoglutarate for Preventing and Managing Intestinal Epithelial Dysfunction.Advances in nutrition (Bethesda, Md.) · 2024Review
99 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsTumor necrosis factor (TNF) increases intestinal epithelial cell shedding and apoptosis, potentially challenging the barrier between the gastrointestinal lumen and internal tissues. We investigated the mechanism of tight junction remodeling and barrier maintenance as well as the roles of cytoskeletal regulatory molecules during TNF-induced shedding.
methodsWe studied wild-type and transgenic mice that express the fluorescent-tagged proteins enhanced green fluorescent protein-occludin or monomeric red fluorescent protein 1-ZO-1. After injection of high doses of TNF (7.5 μg intraperitoneally), laparotomies were performed and segments of small intestine were opened to visualize the mucosa by video confocal microscopy. Pharmacologic inhibitors and knockout mice were used to determine the roles of caspase activation, actomyosin, and microtubule remodeling and membrane trafficking in epithelial shedding.
resultsChanges detected included redistribution of the tight junction proteins ZO-1 and occludin to lateral membranes of shedding cells. These proteins ultimately formed a funnel around the shedding cell that defined the site of barrier preservation. Claudins, E-cadherin, F-actin, myosin II, Rho-associated kinase (ROCK), and myosin light chain kinase (MLCK) were also recruited to lateral membranes. Caspase activity, myosin motor activity, and microtubules were required to initiate shedding, whereas completion of the process required microfilament remodeling and ROCK, MLCK, and dynamin II activities.
conclusionsMaintenance of the epithelial barrier during TNF-induced cell shedding is a complex process that involves integration of microtubules, microfilaments, and membrane traffic to remove apoptotic cells. This process is accompanied by redistribution of apical junctional complex proteins to form intercellular barriers between lateral membranes and maintain mucosal 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.