AhR activation protects intestinal epithelial barrier function through regulation of Par-6.
AhR activation protects intestinal epithelial barrier function through regulation of Par-6.
复制标题
AhR 激活通过调节 Par-6 保护肠上皮屏障功能
DOI：
10.1007/s10735-018-9784-1
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发表时间：
2018
影响因子：
3.2
通讯作者：
Yang Hua
中科院分区：
文献类型：
--
作者：
Yu Kun;Ma Yuanhang;Zhang Zhicao;Fan Xin;Li Teming;Li Liangzi;Xiao Weidong;Cai Yujiao;Sun Lihua;Xu Pengyuan;Yu Min;Yang Hua
Par复合物（Par-6/Par-3/aPKC）通过调节上皮连接的形成在维持肠屏障功能中起关键作用。芳香烃受体（AhR）已被证明是肠道内稳态的重要调节剂。在这项研究中，我们研究了AhR激活对Par复合物的调节作用。6-甲酰吲哚并（3，2-B）咔唑（FICZ）激活AhR抑制葡聚糖硫酸钠（DSS）诱导的结肠炎小鼠模型中Par复合物的异常表达。在T84细胞中，Par-6的过表达导致肠屏障功能障碍。AhR激活可防止脂多糖（LPS）诱导的肠上皮屏障功能障碍和Par-6表达增加。FICZ对Par-3和aPKC的表达无明显影响。此外，AhR激活可通过抑制激活蛋白-2 γ（Ap-2γ）的表达来减轻LPS诱导的Par-6的升高。这些结果揭示了AhR激活通过抑制Par-6表达对LPS诱导的肠上皮屏障功能破坏的保护作用。我们的研究结果为AhR在肠道屏障功能中的保护作用提供了新的见解。
The Par complex (Par-6/Par-3/aPKC) plays a key role in the maintenance of the intestinal barrier function through the regulation of epithelial junction formation. The aryl hydrocarbon receptor (AhR) has been shown to be an important regulator for intestinal homeostasis. In this study, we investigated the role of the AhR activation on the regulation of Par complex. AhR activation by 6-formylindolo (3,2-b) carbazole (FICZ) represses the abnormal expression of the Par complex in a mouse model of dextran sulphate sodium (DSS)-induced colitis. In T84 cells, overexpression of Par-6 causes intestinal barrier dysfunction. Lipopolysaccharide (LPS)-induced intestinal epithelial barrier dysfunction and increase in Par-6 expression was prevented by AhR activation. However, FICZ did not alter the expression of Par-3 or aPKC. Furthermore, AhR activation alleviated LPS-induced increase of Par-6 through repressing the expression of activating protein-2γ (Ap-2γ). These results reveal the protective effects of AhR activation on LPS induced disruption of intestinal epithelial barrier function through suppressing the expression of Par-6 expression. Our findings provide novel insights into the protective role of AhR in intestinal barrier function.