FoxO1 regulates TLR4/MyD88/MD2-NF-κB inflammatory signalling in mucosal barrier injury of inflammatory bowel disease |
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Authors: | Chenyang Han Li Guo Yongjia Sheng Yi Yang Jin Wang Yanling Gu Wenyan Li Xiaohong Zhou Qingcai Jiao |
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Institution: | 1. State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing, China;2. Department of Center Laboratory, The Second Affiliated Hospital of Jiaxing University, Jiaxing, China;3. Department of pharmacy, The Second Affiliated Hospital of Jiaxing University, Jiaxing, China;4. Department of gastroenterology, The Second Affiliated Hospital of Jiaxing University, Jiaxing, China |
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Abstract: | In this study, FoxO1 transgenic mice (transgenic, FoxO1-Tg) and C57BL/6 wild-type (wild-type, FoxO1-WT) mice were used to establish chronic colitis by drinking water containing dextran sulphate sodium (DSS). Afterwards, we observed the life changes in mice and assessed the pathological changes by H&E tissue staining. In addition, the TLR4/MyD88/MD2-NF-κB inflammatory signals were detected. As a result, under DSS treatment, the activation level of TLR4/MyD88/MD2-NF-κB inflammatory signal was higher in FoxO1-Tg mice than that in FoxO1-WT mice. Meanwhile, the intestinal mucosal tissue damage was more severe, the down-regulation of tight junction protein level was more significant and the life quality was decreased to a higher degree in FoxO1-Tg mice compared with those in FoxO1-WT mice. Caco-2 cells were used to mimic the intestinal mucosal barrier model for in vitro assays. In addition, lentiviral packaging FoxO1 overexpressing plasmid was transfected into Caco-2 cells for FoxO1 overexpression. TNF-α intervention was performed for intestinal mucosal inflammatory response model. Consequently, the down-regulation of FoxO1 inhibited the activation of TLR4/MyD88/MD2-NF-κB inflammatory signal, decreased the mucosal barrier permeability and up-regulated the expression of tight junction protein. By contrast, the overexpression of FoxO1 increased the mucosal barrier permeability and down-regulated the level of tight junction protein. |
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