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In vivo analysis of intestinal epithelial barrier maintenance, regulation, and repair.

机译：体内分析肠上皮屏障的维持，调节和修复。

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摘要

Epithelial surfaces function to define the boundary between various tissue compartments. The intestinal epithelium is unique because it must provide a barrier between the harsh environment of the lumen of the intestine and the rest of the body, but must also maintain selective permeability to allow for nutrient and water transport across the mucosa. A functional epithelial barrier is critical to intestinal homeostasis. The tight junction seals the space between epithelial cells and is the main determinant of paracellular permeability. Numerous intestinal disorders are characterized by increased paracellular permeability, or barrier dysfunction.I therefore developed live animal imaging techniques to examine tight junction morphology and determine the mechanisms by which epithelial barrier function is maintained or restored in three increasingly severe models of barrier loss in vivo: (1) cytokine-induced barrier dysfunction, (2) cytokine-induced single cell shedding, and (3) epithelial wound closure. These are the first images of tight junction protein trafficking and remodeling in vivo in real time (Supplementary files videos 1-4).I have discovered important roles for caveolar endocytosis, vesicular trafficking, and cytoskeletal regulation. The mechanistic understanding of the process occurring in live animals is an advancement over previous in vitro and ex vivo studies. These studies have furthered understanding of tight junction regulation and barrier maintenance during physiological and pathophysiological events that could previously only be investigated using in vitro and ex vivo systems.
机译：上皮表面的作用是限定各种组织隔室之间的边界。肠上皮细胞是独特的，因为它必须在肠腔的苛刻环境与身体其余部分之间提供屏障，但还必须保持选择性的渗透性，以允许营养物质和水通过粘膜运输。功能性上皮屏障对于肠道稳态至关重要。紧密连接密封了上皮细胞之间的空间，并且是决定细胞旁通透性的主要因素。许多肠道疾病的特征是副细胞通透性增加或屏障功能障碍，因此我开发了活体动物成像技术来检查紧密连接形态并确定在三种越来越严重的体内屏障丧失模型中维持或恢复上皮屏障功能的机制： （1）细胞因子诱导的屏障功能障碍；（2）细胞因子诱导的单细胞脱落；（3）上皮伤口闭合。这些是体内紧密连接蛋白的实时运输和重塑的第一张图像（补充文件视频1-4）。我发现了小窝内吞作用，囊泡运输和细胞骨架调节具有重要作用。对活体动物发生过程的机理的理解是对先前的体外和离体研究的一种进步。这些研究进一步了解了生理和病理生理事件中紧密连接的调控和屏障的维持，以前只能使用体外和离体系统进行研究。

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  • 作者

    Marchiando, Amanda M.;

  • 作者单位

    The University of Chicago.;

  • 授予单位 The University of Chicago.;
  • 学科 Biology Cell.
  • 学位 Ph.D.
  • 年度 2010
  • 页码 177 p.
  • 总页数 177
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 宗教;
  • 关键词

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