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.
Highlights
Inflammatory bowel disease (IBD) is a type of inflammatory disease that occurs in the digestive tract, with chronic and recurrent course, which can be mainly divided into Crohn's disease (CD) and ulcerative colitis (UC)
The clinical manifestations of IBD include persistent or recurrent diarrhoea, mucopurulent bloody stool accompanied with abdominal pain, with disease course over 4-6 weeks
The clinical diagnosis of IBD is mainly confirmed by endoscopy
Summary
Inflammatory bowel disease (IBD) is a type of inflammatory disease that occurs in the digestive tract, with chronic and recurrent course, which can be mainly divided into Crohn's disease (CD) and ulcerative colitis (UC). The occurrence of IBD mainly damages the local mucosal structure, which is characterized by the loss of tight junction proteins, the damage of intestinal epithelial cells and the destruction of villus structure, among which, local inflammatory response plays an important role.[3,4]. Our team has found that the expression of FoxO1, a transcription factor, is increased in the intestinal tissue of patients with IBD. The expression of FoxO1 and TLR4 is high in IBD. Previous studies have reported the association between TLR4 and FoxO1 in anti-inflammatory response.[8]. Animal experiments conform to the ethical norms of animal experiments and the relevant provisions of animal welfare All patients or their family members signed written informed consent and follow-up consent at the time of initial diagnosis. The resected tissue was washed with PBS for three times, fixed with 4% paraformaldehyde and embedded with paraffin for further analysis
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