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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Acknowledgements
This research was supported by Grants from the National Natural Science Foundation of China (NSFC 81330013 to H.Y., NSFC 81501661 to M.Y., NSFC 81770524 and 81470803 to W.D.X, NSFC 81370054 to Y.J.C.), Innovative Research Team of Ministry of Education of China (IRT_17R16 to H.Y.) and this work was also supported by the Program of Yunnan academican and expert workstation (2015-2).
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Yu, K., Ma, Y., Zhang, Z. et al. AhR activation protects intestinal epithelial barrier function through regulation of Par-6. J Mol Hist 49, 449–458 (2018). https://doi.org/10.1007/s10735-018-9784-1
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DOI: https://doi.org/10.1007/s10735-018-9784-1