ArticleInternational journal of molecular sciences2020
Leptin Downregulates Angulin-1 in Active Crohn's Disease via STAT3.
Article in International journal of molecular sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 20 citations in OpenAlex.
- Tight junction structure, assembly and (dys)function.Nature reviews. Molecular cell biology · 2026Review
- Characterization of intestinal immune responses in generalized human and murine lipodystrophy.The Journal of clinical investigation · 2026Article
- Leptin decreases Th17/Treg ratio to facilitate neuroblastoma via inhibiting long-chain fatty acid catabolism in tumor cells.Oncoimmunology · 2025Article
- Tight Junction Proteins and Blood-brain Barrier Integrity in Pediatric Obsessive-compulsive Disorder: A Study on Claudin-5, Claudin-12, Occludin, Tricellulin, and Angulin-1.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2025Article
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- Dysfunction of epithelial permeability barrier induced by HMGB1 in 2.5D cultures of human epithelial cells.Tissue barriers · 2022Review
- JAK-STAT Pathway Regulation of Intestinal Permeability: Pathogenic Roles and Therapeutic Opportunities in Inflammatory Bowel Disease.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Expression of tricellular tight junction proteins and the paracellular macromolecule barrier are recovered in remission of ulcerative colitis.BMC gastroenterology · 2021Article
- Editorial: Loss of Epithelial Barrier Integrity in Inflammatory Diseases: Cellular Mediators and Therapeutic Targets.Frontiers in medicine · 2021Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Crohn's disease (CD) has an altered intestinal barrier function, yet the underlying mechanisms remain to be disclosed. The tricellular tight junction protein tricellulin is involved in the maintenance of the paracellular macromolecule barrier and features an unchanged expression level in CD but a shifted localization. As angulins are known to regulate the localization of tricellulin, we hypothesized the involvement of angulins in CD. Using human biopsies, we found angulin-1 was downregulated in active CD compared with both controls and CD in remission. In T84 and Caco-2 monolayers, leptin, a cytokine secreted by fat tissue and affected in CD, decreased angulin-1 expression. This effect was completely blocked by STAT3 inhibitors, Stattic and WP1066, but only partially by JAK2 inhibitor AG490. The effect of leptin was also seen at a functional level as we observed in Caco-2 cells an increased permeability for FITC-dextran 4 kDa indicating an impaired barrier against macromolecule uptake. In conclusion, we were able to show that in active CD angulin-1 expression is downregulated, which leads to increased macromolecule permeability and is inducible by leptin via STAT3. This suggests that angulin-1 and leptin secretion are potential targets for intervention in CD to restore the impaired intestinal barrier.
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