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Aryl hydrocarbon receptor utilises cellular zinc signals to maintain the gut epithelial barrier

Zinc and plant-derived ligands of the aryl hydrocarbon receptor (AHR) are dietary components affecting intestinal epithelial barrier function. Here, we explore whether zinc and the AHR pathway are linked. We show that dietary supplementation with an AHR pre-ligand offers protection against inflammat...

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Autores principales: Hu, Xiuchuan (Lucas), Xiao, Wenfeng, Lei, Yuxian, Green, Adam, Lee, Xinyi, Maradana, Muralidhara Rao, Gao, Yajing, Xie, Xueru, Wang, Rui, Chennell, George, Basson, M. Albert, Kille, Pete, Maret, Wolfgang, Bewick, Gavin A., Zhou, Yufeng, Hogstrand, Christer
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10480478/
https://www.ncbi.nlm.nih.gov/pubmed/37669965
http://dx.doi.org/10.1038/s41467-023-41168-y
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author Hu, Xiuchuan (Lucas)
Xiao, Wenfeng
Lei, Yuxian
Green, Adam
Lee, Xinyi
Maradana, Muralidhara Rao
Gao, Yajing
Xie, Xueru
Wang, Rui
Chennell, George
Basson, M. Albert
Kille, Pete
Maret, Wolfgang
Bewick, Gavin A.
Zhou, Yufeng
Hogstrand, Christer
author_facet Hu, Xiuchuan (Lucas)
Xiao, Wenfeng
Lei, Yuxian
Green, Adam
Lee, Xinyi
Maradana, Muralidhara Rao
Gao, Yajing
Xie, Xueru
Wang, Rui
Chennell, George
Basson, M. Albert
Kille, Pete
Maret, Wolfgang
Bewick, Gavin A.
Zhou, Yufeng
Hogstrand, Christer
author_sort Hu, Xiuchuan (Lucas)
collection PubMed
description Zinc and plant-derived ligands of the aryl hydrocarbon receptor (AHR) are dietary components affecting intestinal epithelial barrier function. Here, we explore whether zinc and the AHR pathway are linked. We show that dietary supplementation with an AHR pre-ligand offers protection against inflammatory bowel disease in a mouse model while protection fails in mice lacking AHR in the intestinal epithelium. AHR agonist treatment is also ineffective in mice fed zinc depleted diet. In human ileum organoids and Caco-2 cells, AHR activation increases total cellular zinc and cytosolic free Zn(2+) concentrations through transcription of genes for zinc importers. Tight junction proteins are upregulated through zinc inhibition of nuclear factor kappa-light-chain-enhancer and calpain activity. Our data show that AHR activation by plant-derived dietary ligands improves gut barrier function at least partly via zinc-dependent cellular pathways, suggesting that combined dietary supplementation with AHR ligands and zinc might be effective in preventing inflammatory gut disorders.
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spelling pubmed-104804782023-09-07 Aryl hydrocarbon receptor utilises cellular zinc signals to maintain the gut epithelial barrier Hu, Xiuchuan (Lucas) Xiao, Wenfeng Lei, Yuxian Green, Adam Lee, Xinyi Maradana, Muralidhara Rao Gao, Yajing Xie, Xueru Wang, Rui Chennell, George Basson, M. Albert Kille, Pete Maret, Wolfgang Bewick, Gavin A. Zhou, Yufeng Hogstrand, Christer Nat Commun Article Zinc and plant-derived ligands of the aryl hydrocarbon receptor (AHR) are dietary components affecting intestinal epithelial barrier function. Here, we explore whether zinc and the AHR pathway are linked. We show that dietary supplementation with an AHR pre-ligand offers protection against inflammatory bowel disease in a mouse model while protection fails in mice lacking AHR in the intestinal epithelium. AHR agonist treatment is also ineffective in mice fed zinc depleted diet. In human ileum organoids and Caco-2 cells, AHR activation increases total cellular zinc and cytosolic free Zn(2+) concentrations through transcription of genes for zinc importers. Tight junction proteins are upregulated through zinc inhibition of nuclear factor kappa-light-chain-enhancer and calpain activity. Our data show that AHR activation by plant-derived dietary ligands improves gut barrier function at least partly via zinc-dependent cellular pathways, suggesting that combined dietary supplementation with AHR ligands and zinc might be effective in preventing inflammatory gut disorders. Nature Publishing Group UK 2023-09-05 /pmc/articles/PMC10480478/ /pubmed/37669965 http://dx.doi.org/10.1038/s41467-023-41168-y Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Hu, Xiuchuan (Lucas)
Xiao, Wenfeng
Lei, Yuxian
Green, Adam
Lee, Xinyi
Maradana, Muralidhara Rao
Gao, Yajing
Xie, Xueru
Wang, Rui
Chennell, George
Basson, M. Albert
Kille, Pete
Maret, Wolfgang
Bewick, Gavin A.
Zhou, Yufeng
Hogstrand, Christer
Aryl hydrocarbon receptor utilises cellular zinc signals to maintain the gut epithelial barrier
title Aryl hydrocarbon receptor utilises cellular zinc signals to maintain the gut epithelial barrier
title_full Aryl hydrocarbon receptor utilises cellular zinc signals to maintain the gut epithelial barrier
title_fullStr Aryl hydrocarbon receptor utilises cellular zinc signals to maintain the gut epithelial barrier
title_full_unstemmed Aryl hydrocarbon receptor utilises cellular zinc signals to maintain the gut epithelial barrier
title_short Aryl hydrocarbon receptor utilises cellular zinc signals to maintain the gut epithelial barrier
title_sort aryl hydrocarbon receptor utilises cellular zinc signals to maintain the gut epithelial barrier
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10480478/
https://www.ncbi.nlm.nih.gov/pubmed/37669965
http://dx.doi.org/10.1038/s41467-023-41168-y
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