芳烃受体利用细胞内锌信号来维持肠道上皮屏障。
Aryl hydrocarbon receptor utilises cellular zinc signals to maintain the gut epithelial barrier.
机构信息
Institute of Pediatrics, Children's Hospital of Fudan University, and the Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Department of Nutritional Sciences, King's College London, London, UK.
出版信息
Nat Commun. 2023 Sep 5;14(1):5431. doi: 10.1038/s41467-023-41168-y.
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 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.
锌和植物来源的芳烃受体 (AHR) 配体是影响肠道上皮屏障功能的饮食成分。在这里，我们探讨了锌和 AHR 途径是否有关联。我们发现，用 AHR 前配体进行饮食补充可以在小鼠模型中预防炎症性肠病，而在肠道上皮缺乏 AHR 的小鼠中则没有这种保护作用。在缺锌饮食喂养的小鼠中，AHR 激动剂治疗也无效。在人类回肠类器官和 Caco-2 细胞中，AHR 激活通过锌转运体基因的转录增加总细胞内锌和细胞质游离 Zn 浓度。通过锌抑制核因子 kappa-轻链增强子和钙蛋白酶活性，上调紧密连接蛋白。我们的数据表明，植物源性饮食配体激活 AHR 通过锌依赖性细胞途径改善肠道屏障功能，这表明联合饮食补充 AHR 配体和锌可能有效预防炎症性肠道疾病。
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