Mechanisms of Epithelial Cell Shedding in the Mammalian Intestine and Maintenance of Barrier Function
Mechanisms of Epithelial Cell Shedding in the Mammalian Intestine and Maintenance of Barrier Function
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DOI：
10.1111/j.1749-6632.2009.04027.x
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发表时间：
2009-05
影响因子：
5.2
通讯作者：
A. J. Watson;C. Duckworth;Yanfang Guan;M. Montrose
中科院分区：
文献类型：
--
作者：
A. J. Watson;C. Duckworth;Yanfang Guan;M. Montrose
肠上皮在肠腔和身体之间形成屏障。该屏障可能受到上皮细胞脱落的高周转的挑战。我们的实验室已经表明，上皮细胞被称为“间隙”的不连续性所打断，这些间隙具有上皮细胞的直径并且没有细胞内容物。至少一部分间隙是由上皮细胞脱落形成的。这些间隙被一种未知物质填充，以维持局部屏障功能。缺口已确定在小鼠体内共聚焦显微镜和在人类共聚焦显微内镜。它们可以通过缺乏细胞核而与杯状细胞区分开来，并且在没有杯状细胞的Math 1 −/−小鼠中发现。TNF-α可增加细胞脱落和间隙形成。在约20%的脱落事件中，TNF-α治疗后屏障功能丧失。这些观察结果表明，细胞脱落部位屏障功能的丧失在上皮通透性增加在发病机制中起作用的肠道疾病中可能是重要的。
The intestinal epithelium forms a barrier between the gut lumen and the body. The barrier is potentially challenged by the high turnover of epithelial cells being shed. Our laboratories have shown that the epithelium is punctuated by discontinuities called “gaps” that have the diameter of an epithelial cell and are devoid of cellular contents. At least a proportion of gaps are formed by the shedding of epithelial cells. These gaps are filled with an unknown substance that maintains local barrier function. Gaps have been identified in the mouse by in vivo confocal microscopy and in humans by confocal endomicroscopy. They can be distinguished from goblet cells by the absence of a nucleus and are found in Math1−/− mice where goblet cells are absent. Cell shedding and gap formation is increased by TNF‐α. Barrier function is lost after TNF‐α in approximately 20% of shedding events. These observations suggest that loss of barrier function at sites of cell shedding may be important in intestinal diseases where an increase in epithelial permeability plays a role in pathogenesis.