ArticleGastroenterology2011
Notch-1 signaling regulates intestinal epithelial barrier function, through interaction with CD4+ T cells, in mice and humans.
Article in Gastroenterology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 85 citations in OpenAlex.
- Plasma lipopolysaccharide-binding protein (LBP), a proxy for intestinal permeability, relates to clinicopathological and immunological disease activity in inflammatory bowel disease patients at diagnosis and during disease course.Journal of Crohn's & colitis · 2026Article
- Activated notch signaling pathway protects the intestinal barrier in DSS-induced colitis by regulating tight junctions.European journal of medical research · 2026Article
- Mucosal DNA methylation reveals immune-related methylation profile and correlates with crohn's disease status.Scientific reports · 2026Article
- Claudin 5 Across the Vascular Landscape: From Blood-Tissue Barrier Regulation to Disease Mechanisms.Cells · 2025Review
- Redefining the Immunobiology of Organ Transplantation for New Clinical Horizons.Scandinavian journal of immunology · 2025Review
- Lacidipine Inhibits NF-κB and Notch Pathways and Mitigates DSS-Induced Colitis.Digestive diseases and sciences · 2024Article
- Mucosal host-microbe interactions associate with clinical phenotypes in inflammatory bowel disease.Nature communications · 2024Article
- Vitamin D/vitamin D receptor protects intestinal barrier against colitis by positively regulating Notch pathway.Frontiers in pharmacology · 2024Article
- Notch1 cortical signaling regulates epithelial architecture and cell-cell adhesion.The Journal of cell biology · 2023Article
- Notch1 cortical signaling regulates epithelial architecture and cell-cell adhesion.bioRxiv : the preprint server for biology · 2023Article
- Proteomic analyses do not reveal subclinical inflammation in fatigued patients with clinically quiescent inflammatory bowel disease.Scientific reports · 2022Article
- Paraprobiotics and Postbiotics ofMicroorganisms · 2022Article
- The Effect of Phenotype and Genotype on the Plasma Proteome in Patients with Inflammatory Bowel Disease.Journal of Crohn's & colitis · 2022Article
- Integrin αEβ7Cell research · 2021Article
- Matrix Metalloproteinase MMP-12 Promotes Macrophage Transmigration Across Intestinal Epithelial Tight Junctions and Increases Severity of Experimental Colitis.Journal of Crohn's & colitis · 2021Article
- Prenylated xanthones from mangosteen (Garcinia mangostana) activate the AhR and Nrf2 pathways and protect intestinal barrier integrity in HT-29 cells.Free radical biology & medicine · 2021Article
- Notch inhibitors induce diarrhea, hypercrinia and secretory cell metaplasia in the human colon.EXCLI journal · 2021Article
- Targeting the Notch Signaling Pathway in Chronic Inflammatory Diseases.Frontiers in immunology · 2021Review
- Claudins: Beyond Tight Junctions in Human IBD and Murine Models.Frontiers in pharmacology · 2021Article
- A Novel PAK1-Notch1 Axis Regulates Crypt Homeostasis in Intestinal Inflammation.Cellular and molecular gastroenterology and hepatology · 2021Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsInteractions between lymphocytes and intestinal epithelial cells occur in the subepithelial space of the gastrointestinal tract. Normal human lamina propria lymphocytes (LPLs) induce differentiation of intestinal epithelial cells. The absence of LPLs in mice, such as in RAG1(-/-) mice, results in defects in epithelial cell differentiation. We investigated the role of lymphoepithelial interactions in epithelial differentiation and barrier function.
methodsWe used adoptive transfer to determine if CD4(+) T cells (CD4(+)CD62L(+)CD45Rb(Hi) and/or CD4(+)CD62L(+)CD45Rb(Lo)) could overcome permeability defect (quantified in Ussing chambers). Immunofluorescence staining was performed to determine expression of cleaved Notch-1, villin, and claudin 5 in colon samples from mice and humans. Caco-2 cells were infected with a lentivirus containing a specific Notch-1 or scrambled short hairpin RNA sequence. Tight junction assembly was analyzed by immunoblot and immunofluorescence analyses, and transepithelial resistance was monitored.
resultsExpression of cleaved Notch-1, villin, or claudin 5 was not detected in RAG1(-/-) colonocytes; their loss correlated with increased intestinal permeability. Transfer of CD45Rb(Hi) and/or CD45Rb(Lo) cells into RAG1(-/-) mice induced expression of cleaved Notch, villin, and claudin 5 in colonocytes and significantly reduced the permeability of the distal colon. Loss of Notch-1 expression in Caco-2 cells correlated with decreased transepithelial resistance and dysregulated expression and localization of tight junction proteins. Levels of cleaved Notch-1 were increased in colonic epithelium of patients with Crohn's disease.
conclusionsLPLs promote mucosal barrier function, which is associated with activation of the Notch-1 signaling pathway. LPLs maintain intestinal homeostasis by inducing intestinal epithelial cell differentiation, polarization, and barrier function.
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