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Article

Leptin Downregulates Angulin-1 in Active Crohn’s Disease via STAT3

1
Institute of Clinical Physiology/Nutritional Medicine, Charité—Universitätsmedizin Berlin, Campus Benjamin Franklin, 12203 Berlin, Germany
2
Department of Gastroenterology, Rheumatology and Infectious Diseases, Charité—Universitätsmedizin Berlin, Campus Benjamin Franklin, 12203 Berlin, Germany
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(21), 7824; https://doi.org/10.3390/ijms21217824
Received: 2 October 2020 / Revised: 19 October 2020 / Accepted: 20 October 2020 / Published: 22 October 2020
(This article belongs to the Special Issue Pathophysiology in Colonic Diseases)
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. View Full-Text
Keywords: leptin; Crohn’s disease; tight junction; angulin-1 leptin; Crohn’s disease; tight junction; angulin-1
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MDPI and ACS Style

Hu, J.-C.E.; Bojarski, C.; Branchi, F.; Fromm, M.; Krug, S.M. Leptin Downregulates Angulin-1 in Active Crohn’s Disease via STAT3. Int. J. Mol. Sci. 2020, 21, 7824. https://doi.org/10.3390/ijms21217824

AMA Style

Hu J-CE, Bojarski C, Branchi F, Fromm M, Krug SM. Leptin Downregulates Angulin-1 in Active Crohn’s Disease via STAT3. International Journal of Molecular Sciences. 2020; 21(21):7824. https://doi.org/10.3390/ijms21217824

Chicago/Turabian Style

Hu, Jia-Chen E., Christian Bojarski, Federica Branchi, Michael Fromm, and Susanne M. Krug 2020. "Leptin Downregulates Angulin-1 in Active Crohn’s Disease via STAT3" International Journal of Molecular Sciences 21, no. 21: 7824. https://doi.org/10.3390/ijms21217824

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