Aryl Hydrocarbon Receptor Activation Modulates Intestinal Epithelial Barrier Function by Maintaining Tight Junction Integrity.
Aryl Hydrocarbon Receptor Activation Modulates Intestinal Epithelial Barrier Function by Maintaining Tight Junction Integrity.
复制标题
芳基烃受体激活通过维持紧密连接完整性来调节肠上皮屏障功能。
DOI：
10.7150/ijbs.22259
复制
发表时间：
2018
影响因子：
9.2
通讯作者：
Yang H
中科院分区：
文献类型：
--
作者：
Yu M;Wang Q;Ma Y;Li L;Yu K;Zhang Z;Chen G;Li X;Xiao W;Xu P;Yang H
芳香烃受体(AhR)的激活参与了肠粘膜内稳态的调控。肠屏障功能障碍导致许多肠道疾病的发生，如炎症性肠病(IBD)。在本研究中，我们探讨了AhR激活在维持肠屏障功能中的作用机制。成年C57BL/6小鼠用葡聚糖硫酸钠(DSS)处理7d，加或不加AhR配体6-甲醛并(3，2-b)咔唑(FICZ)。我们发现，FICZ激活AhR可以减轻DSS诱导的小鼠结肠粘膜TJ蛋白表达的减少。此外，FICZ诱导的AhR激活也显著抑制了DSS诱导的结肠炎小鼠MLC磷酸化和MLCK表达的增加。在体外实验中，肿瘤坏死因子-α(TN-α)/干扰素-γ(干扰素-γ)联合作用于Caco-2细胞48h。AHR激活可阻止肿瘤坏死因子-α/干扰素-γ诱导的TER下降和Caco-2单层TJ的形态破坏。它还通过抑制NF-αB p65信号通路，抑制肿瘤坏死因子-γ/干扰素-κ诱导的MLCK表达和MLC磷酸化。因此，AhR激活因子有可能作为治疗IBD患者的药物。
Activation of Aryl hydrocarbon receptor (AhR) is involved in the control of intestinal mucosal homeostasis. Intestinal barrier dysfunction contributes to the development of many intestinal diseases, such as inflammatory bowel disease (IBD). In this study, we investigated the mechanisms of AhR activation in the maintenance of intestinal barrier function. Adult C57BL/6 mice were treated with dextran sulphate sodium (DSS) for 7 days, with or without 6-Formylindolo(3,2-b)carbazole (FICZ), a ligand of AhR. We found that AhR activation by FICZ attenuated the decreased TJ protein expression in the colonic mucosa of the DSS-induced mice. Further, the increase of both MLC phosphorylation and MLCK expression in the mice with DSS-induced colitis was also significantly inhibited by FICZ induced AhR activation. For in vitro experiments, Caco-2 cells were treated with tumour necrosis factor alpha (TNF-α)/interferon gamma (IFN-γ) for 48 h, with or without FICZ. AhR activation prevented TNF-α/IFN-γ-induced decrease in TER and morphological disruption of the TJs in Caco-2 monolayers. It also inhibited TNF-α/IFN-γ-induced increase in MLCK expression and MLC phosphorylation by suppression of NF-κB p65 signaling pathway. Thus, AhR-activating factors might have potential as therapeutic agents for the treatment of patients with IBD.
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DOI：
10.1152/ajpgi.00412.2004
发表时间：
2005-03-01
影响因子：
4.5
作者：
Ma, TY;Boivin, MA;Said, HM
通讯作者：
Said, HM
影响因子：
29.4
作者：
Monteleone, Ivan;Rizzo, Angelamaria;Monteleone, Giovanni
通讯作者：
Monteleone, Giovanni
影响因子：
5.1
作者：
Farmahin, Reza;Crump, Doug;Kennedy, Sean W.
通讯作者：
Kennedy, Sean W.
影响因子：
5.2
作者：
Cunningham KE;Turner JR
通讯作者：
Turner JR
影响因子：
4.8
作者：
Graham, W. Vallen;Wang, Fengjun;Turner, Jerrold R.
通讯作者：
Turner, Jerrold R.