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首页> 外文期刊>Infection and immunity >Critical Roles of Notch and Wnt/β-Catenin Pathways in the Regulation of Hyperplasia and/or Colitis in Response to Bacterial Infection
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Critical Roles of Notch and Wnt/β-Catenin Pathways in the Regulation of Hyperplasia and/or Colitis in Response to Bacterial Infection

机译：Notch和Wnt /β-Catenin途径在细菌感染反应中增生和/或结肠炎调节中的关键作用

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Notch and Wnt/β-catenin signals play essential roles in intestinal development and homeostasis. Citrobacter rodentium induces transmissible murine colonic hyperplasia (TMCH) and various degrees of inflammation, depending upon the genetic background. We aimed at delineating the role of the Notch and Wnt/β-catenin pathways in the regulation of colonic crypt hyperplasia and/or colitis following C. rodentium infection. During TMCH, relative levels of the Notch intracellular domain (NICD) increased significantly, along with increases in Jagged-1 and Hes-1 coinciding with the progression and regression phases of hyperplasia. Blocking of Notch signaling with dibenzazepine (DBZ) for 5 days before the onset of hyperplasia also blocked Wnt/β-catenin signaling. Targeting the Notch pathway for 5 days after the onset of hyperplasia failed to inhibit Wnt/β-catenin-regulated crypt hyperplasia. Chronic DBZ administration for 10 days blocked both Notch and Wnt signaling, disrupted the intestinal barrier, and induced colitis. Core-3?/? mice, which are defective in mucin secretion and are susceptible to experimental triggers of colitis, also exhibited significant colitis in response to C. rodentium plus DBZ. Chronic DBZ administration in these mice did not result in depletion of the putative stem cell marker doublecortin-like kinase-1 (DCLK1) in the crypts. Dietary bael (Aegle marmelos) extract (4%) and curcumin (4%) restored signaling via the Notch and Wnt/β-catenin pathways, thereby promoting crypt regeneration, and also replenished the mucus layer, leading to amelioration of C. rodentium- and DBZ-induced colitis in NIH:Swiss mice. Thus, the balancing act between cell proliferation and mucus production to restore barrier integrity seems to depend upon the interplay between the Wnt/β-catenin and Notch pathways in the TMCH model.
机译：Notch和Wnt /β-catenin信号在肠道发育和体内平衡中起重要作用。啮齿类柠檬酸杆菌可引起传播性鼠结肠增生（TMCH）和各种程度的炎症，具体取决于遗传背景。我们旨在描述Notch和Wnt /β-catenin途径在啮齿类念珠菌感染后结肠隐窝增生和/或结肠炎的调节中的作用。在TMCH期间，Notch细胞内区域（NICD）的相对水平显着增加，同时Jagged-1和Hes-1的增加与增生的进展和消退阶段相吻合。在增生开始之前用地苯二氮卓（DBZ）阻断Notch信号传导达5天，也阻断了Wnt /β-catenin信号传导。在增生发作后靶向Notch通路5天不能抑制Wnt /β-catenin调节的隐窝增生。连续10天的DBZ长期给药可阻断Notch和Wnt信号传导，破坏肠屏障，并诱发结肠炎。 Core-3 ？/？小鼠的粘蛋白分泌有缺陷，易受实验性结肠炎的影响，但对啮齿类念珠菌和DBZ的反应也表现出明显的结肠炎。在这些小鼠中长期给予DBZ并不会导致隐窝中假定的干细胞标志物双皮质素样激酶1（DCLK1）耗竭。饮食中的ba（Aegle marmelos）提取物（4％）和姜黄素（4％）通过Notch和Wnt /β-catenin途径恢复了信号传导，从而促进了隐窝再生，并补充了粘液层，从而改善了啮齿类念珠菌。和DBZ诱发的NIH：Swiss小鼠结肠炎。因此，细胞增殖和粘液产生之间的平衡作用恢复屏障完整性似乎取决于TMCH模型中Wnt /β-catenin和Notch途径之间的相互作用。

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