Department of General Surgery, Xinqiao Hospital, Army Military Medical University, Chongqing, China.
Department of General Surgery, Sixth Medical Center of PLA General Hospital, Beijing, China.
Biochem Biophys Res Commun. 2019 Jun 18;514(1):180-186. doi: 10.1016/j.bbrc.2019.04.136. Epub 2019 Apr 24.
The intestinal inflammation induces disruption of the intestinal barrier function and leads to bacteria invasion. Accumulating evidences revealed that the aryl hydrocarbon receptor (AhR) plays a vital role in maintaining the intestinal barrier function. However, the precise mechanism remains to be unclear.
Adult C57BL/6J mice were randomly divided into three groups: Sham, DSS and DSS + 6-formylindolo (3, 2-b) carbazole (FICZ)group. The colons and epithelial cell were harvested for histological examination, pro-inflammatory cytokines detection, bacterial load analysis, immunohistochemistry and Muc2 protein analysis. Under physiological condition, AhRKO model and FICZ treatment were used to evaluate the roles of AhR in the differentiation of goblet cells and the expression of Muc2 in mice. In vitro, we used HT29 mol to research the signaling pathway.
AhR activation by FICZ could increase the Muc2 expression and the number of goblet cells and reduce bacterial infiltration to ameliorate DSS-induced Colitis. Under physiological conditions, the treatment of FICZ promote the differentiation of goblet cell and the expression of Muc2 and inhibit the notch-signaling. Genetic deletion of AhR led to the loss of goblet cells and the decrease of Muc2 expression and enhance the notch-signaling. In HT29 cells, the differentiation of goblet cell meditated by AhR can be abolished by the inhibitor of AhR, pErk1/2 and knocking-down AhR.
FICZ promoted the differentiation of goblet cell through AhR-pErk1/2 signaling pathway and ameliorate DSS-induced Colitis.
肠道炎症会破坏肠道屏障功能，导致细菌入侵。越来越多的证据表明，芳香烃受体（AhR）在维持肠道屏障功能方面起着至关重要的作用。然而，其确切的机制仍不清楚。
将成年 C57BL/6J 小鼠随机分为三组：Sham、DSS 和 DSS+6-Formylindolo（3,2-b）carbazole（FICZ）组。采集结肠和上皮细胞进行组织学检查、促炎细胞因子检测、细菌负荷分析、免疫组织化学和 Muc2 蛋白分析。在生理条件下，使用 AhRKO 模型和 FICZ 处理来评估 AhR 在小鼠杯状细胞分化和 Muc2 表达中的作用。在体外，我们使用 HT29 细胞来研究信号通路。
FICZ 激活 AhR 可增加 Muc2 表达和杯状细胞数量，减少细菌浸润，从而改善 DSS 诱导的结肠炎。在生理条件下，FICZ 的处理促进了杯状细胞的分化和 Muc2 的表达，并抑制了 Notch 信号。AhR 的基因缺失导致杯状细胞丢失和 Muc2 表达减少，并增强了 Notch 信号。在 HT29 细胞中，AhR 介导的杯状细胞分化可被 AhR 抑制剂、pErk1/2 和 AhR 敲低所抑制。
FICZ 通过 AhR-pErk1/2 信号通路促进杯状细胞分化，改善 DSS 诱导的结肠炎。
