AhR activation protects intestinal epithelial barrier function through regulation of Par-6 |
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Authors: | Kun Yu Yuanhang Ma Zhicao Zhang Xin Fan Teming Li Liangzi Li Weidong Xiao Yujiao Cai Lihua Sun Pengyuan Xu Min Yu Hua Yang |
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Institution: | 1.Department of General Surgery, Xinqiao Hospital,Third Military Medical University,Chongqing,China;2.Department of Gastrointestinal Surgery,The Second Affiliated Hospital of Kunming Medical University,Kunming,China |
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Abstract: | 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. |
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