ArticleJournal of Crohn's & colitis2017
Genetic Mouse Models with Intestinal-Specific Tight Junction Deletion Resemble an Ulcerative Colitis Phenotype.
Article in Journal of Crohn's & colitis, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 53 citations in OpenAlex.
- Clinical effects of ursodeoxycholic acid on patients with ulcerative colitis may improve via the regulation of IL-23-IL-17 axis and the changes of the proportion of intestinal microflora.Saudi journal of gastroenterology : official journal of the Saudi Gastroenterology AssociationTrial
- Phenotypic switching of gastrointestinal smooth muscle cells and the regulatory role of macrophages: a literature review.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Isoliquiritigenin alleviates ulcerative colitis by enhancing the intestinal barrier and improving intestinal microbiota via inhibiting the TLR4/MyD88/NF-κB pathway.Scientific reports · 2026Article
- Ion transport and epithelial barrier dysfunction in experimental models of ulcerative colitis.American journal of physiology. Gastrointestinal and liver physiology · 2025Review
- Drug Repurposing to Inhibit Oncostatin M in Crohn's Disease.Molecules (Basel, Switzerland) · 2025Article
- [Swertiamarin ameliorates 2, 4, 6-trinitrobenzenesulfonic acid-induced colitis in mice by inhibiting intestinal epithelial cell apoptosis].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024Article
- Establishment and Evaluation of a Mouse Model of Experimental Ulcerative Colitis Induced by the Gavage Administration of Dextran Sulfate Sodium.Biomedicines · 2024Article
- Genetically predicted gut microbiota mediate the association between plasma lipidomics and primary sclerosing cholangitis.BMC gastroenterology · 2024Article
- The mechanism of traditional medicine in alleviating ulcerative colitis: regulating intestinal barrier function.Frontiers in pharmacology · 2023Review
- High-fat diet induces intestinal mucosal barrier dysfunction in ulcerative colitis: emerging mechanisms and dietary intervention perspective.American journal of translational research · 2023Review
- Hemin Ameliorates the Inflammatory Activity in the Inflammatory Bowel Disease: A Non-Clinical Study in Rodents.Biomedicines · 2022Article
- Anti-Inflammatory Effect of Topiramate in a Chronic Model of TNBS-Induced Colitis.International journal of molecular sciences · 2022Article
- Effects of Ganoderic Acid A on Gastrointestinal Motility and Brain-Gut Peptide in Rats with Functional Dyspepsia.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- The neglected biliary mucus and its phosphatidylcholine content: a putative player in pathogenesis of primary cholangitis-a narrative review article.Annals of translational medicine · 2021Review
- Pancreastatin Reduces Alternatively Activated Macrophages, Disrupts the Epithelial Homeostasis and Aggravates Colonic Inflammation. A Descriptive Analysis.Biomedicines · 2021Article
- Milk Exosomes Prevent Intestinal Inflammation in a Genetic Mouse Model of Ulcerative Colitis: A Pilot Experiment.Inflammatory intestinal diseases · 2020Article
- Pioglitazone Attenuates Experimental Colitis-Associated Hyperalgesia through Improving the Intestinal Barrier Dysfunction.Inflammation · 2020Article
- Sini San ameliorates duodenal mucosal barrier injury and low‑grade inflammation via the CRF pathway in a rat model of functional dyspepsia.International journal of molecular medicine · 2020Article
- Mucins in Intestinal Mucosal Defense and Inflammation: Learning From Clinical and Experimental Studies.Frontiers in immunology · 2020Review
- Phosphatidylcholine Passes by Paracellular Transport to the Apical Side of the Polarized Biliary Tumor Cell Line Mz-ChA-1.International journal of molecular sciences · 2019Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
aimsA key pathogenetic feature of ulcerative colitis [UC] is an intrinsic low mucus phosphatidylcholine[PC] content. Recently, a paracellular transport for PC across tight junctions[TJs] was described, suggesting TJ disturbance as a cause of diminished luminal PC transport. Therefore, we aimed to generate mutant mice with TJ deletion to evaluate whether a UC phenotype developed.
methodsCL57BL/6 control wild-type mice were compared to mutant mice with tamoxifen-induced villin-Cre-dependent intestinal deletion of kindlin 1 and 2.
resultsElectron microscopy of mucosal biopsies obtained from both mutants before overt inflammation following only 2 days of tamoxifen exposure revealed a defective TJ morphology with extended paracellular space and, by light microscopy, expanded mucosal crypt lumina. PC secretion into mucus was reduced by >65% and the mucus PC content dropped by >50%, causing a >50 % decrease of mucus hydrophobicity in both mutants. Consequently, the microbiota was able to penetrate the submucosa. After 3 days of tamoxifen exposure, intestinal inflammation was present in both mutants, with loose bloody stools as well as macroscopic and histological features of colitis. Oral PC supplementation was able to suppress inflammation. By analogy, colonic biopsies obtained from patients with UC in remission also showed a defective epithelium with widened intercellular clefts, and enlarged crypt luminal diameters with functionally impaired luminal PC secretion.
conclusionsGenetic mouse models with intestinal deletion of kindlin 1 and 2 resulted in TJ deletion and revealed pathophysiological features of impaired PC secretion to the mucus leading to mucosal inflammation compatible with human UC.
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