Aryl hydrocarbon receptor activation alleviates dextran sodium sulfate-induced colitis through enhancing the differentiation of goblet cells
Aryl hydrocarbon receptor activation alleviates dextran sodium sulfate-induced colitis through enhancing the differentiation of goblet cells
复制标题
芳基烃受体激活通过增强杯状细胞的分化减轻葡聚糖硫酸钠诱导的结肠炎
DOI：
10.1016/j.bbrc.2019.04.136
复制
发表时间：
2019
影响因子：
3.1
通讯作者：
Yang Hua
中科院分区：
文献类型：
--
作者：
Yin Jiuheng;Yang Kunqiu;Zhou Chao;Xu Pengyuan;Xiao Weidong;Yang Hua
研究背景肠道炎症可导致肠道屏障功能的破坏，导致细菌的侵入。越来越多的证据表明，芳香烃受体（AhR）在维持肠道屏障功能中起着重要作用。方法成年C57 BL/6 J小鼠随机分为假手术组、DSS组和DSS + 6-甲酰吲哚并（3，2-B）咔唑（FICZ）组。收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Muc 2蛋白分析。在生理条件下，采用AhRKO模型和FICZ处理，观察AhR对小鼠杯状细胞分化和Muc 2表达的影响。结果FICZ激活AhR后，可增加Muc 2的表达，增加杯状细胞的数量，减少细菌浸润，从而改善DSS诱导的结肠炎。在生理条件下，FICZ处理促进杯状细胞的分化和Muc 2的表达，抑制Notch信号通路。AhR基因缺失导致杯状细胞的缺失和Muc 2表达的减少，Notch信号增强。在HT 29细胞中，AhR介导的杯状细胞分化可被AhR抑制剂pErk 1/2和敲低AhR所阻断。结论FICZ通过AhR-pErk 1/2信号通路促进杯状细胞分化，改善DSS诱导的结肠炎。
BackgroundThe 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.MethodsAdult 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.ResultsAhR 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.ConclusionFICZ promoted the differentiation of goblet cell through AhR-pErk1/2 signaling pathway and ameliorate DSS-induced Colitis.