PDF(Pubmed)
Abstract：
Intestinal homeostasis depends on interactions between the intestinal epithelium, the immune system and the microbiota. Because of these complicated connections, there are many problems that need to be solved. Current research has indicated that genes targeted by Wnt signaling are responsible for controlling intestinal stem cell fate and for modulating intestinal homeostasis. Our data show that loss of frizzled 7 (Fzd7), an important element in Wnt signaling, interrupts the differentiation of mouse intestinal stem cells into absorptive progenitors instead of secretory progenitors (precursors of goblet and Paneth cells). The alteration in canonical Wnt and Notch signaling pathways interrupts epithelial homeostasis, resulting in a decrease in physical protection in the intestine. Several phenotypes in our Fzd7-deleted model were similar to the features of enterocolitis, such as shortened intestines, decreased numbers of goblet cells and Paneth cells, and severe inflammation. Additionally, loss of Fzd7 exacerbated the defects in a chemical-induced colitis model and could initiate tumorigenesis. These findings may provide important information for the discovery of efficient therapeutic methods to treat enterocolitis and related cancers in the intestines.
摘要：
肠稳态取决于肠上皮之间的相互作用，免疫系统,和微生物群。因为这些复杂的联系，有许多问题需要解决。目前的研究表明，Wnt信号传导下的靶基因负责控制肠道干细胞命运和调节肠道稳态。正如我们的数据所示，Frizzled-7（Fzd7）的损失，Wnt信号中的一个重要元素，中断肠干细胞分化为吸收祖细胞而不是分泌祖细胞（杯状和Paneth细胞的前体）。经典Wnt和Notch信号通路的改变中断了上皮稳态，导致肠道物理保护降低。Fzd7缺失模型中的几种表型与小肠结肠炎的特征相似，如缩短的肠，杯状细胞和潘氏细胞的数量减少，严重的炎症。此外,Fzd7的缺失加剧了化学诱导结肠炎模型的缺陷，并可能引发肿瘤发生。这些发现可能为发现治疗小肠结肠炎和相关肠道癌症的有效治疗方法提供重要信息。
