Dynamic Regulation of Epithelial Cell Fate and Barrier Function by Intercellular Junctions
Dynamic Regulation of Epithelial Cell Fate and Barrier Function by Intercellular Junctions
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DOI：
10.1111/j.1749-6632.2009.04025.x
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发表时间：
2009-01-01
期刊：
影响因子：
--
通讯作者：
Nusrat, Asma
中科院分区：
文献类型：
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作者：
Koch, Stefan;Nusrat, Asma
在肠中，单层上皮细胞有效地将潜在有害的管腔内容物与下层组织分离。肠道的病理性疾病，如炎症性肠病，突出了完整粘膜层的重要性，其中上皮屏障的破坏导致粘膜下组织区室的严重炎症。上皮屏障功能由严格调节的细胞间连接提供，细胞间连接由组织在离散的、空间受限的复合物中的过多的膜相关和跨膜蛋白组成。传统上，已知这些复合物是流体和小分子的动态密封，以及通过将细胞-细胞接触锚定到细胞骨架来提供机械强度。然而，连接复合物本身并不只是作为简单的门和适配器，而是可以将细胞外刺激传递到上皮并启动细胞反应，如分化和凋亡。在这篇综述中，我们将重点介绍我们小组和其他人最近的研究，这些研究讨论了连接蛋白如何促进由外向内的信号传导和调节上皮细胞的命运。解开上皮细胞和它们的细胞间连接之间的复杂串扰对于理解上皮屏障功能如何在体内维持是必不可少的，并且可能为治疗肠道炎性疾病提供新的策略。
In the intestine, a single layer of epithelial cells effectively separates potentially harmful luminal content from the underlying tissue. The importance of an intact mucosal layer is highlighted by pathological disorders of the gut such as inflammatory bowel disease, in which disruption of the epithelial barrier leads to severe inflammation of the submucosal tissue compartments. Epithelial barrier function is provided by tightly regulated intercellular junctions, which consist of a plethora of membrane-associated and transmembrane proteins organized in discreet, spatially restricted complexes. Classically, these complexes are known to be dynamic seals for fluids and small molecules, as well as to provide mechanical strength by anchoring cell-cell contacts to the cytoskeleton. Rather than just acting as simple gates and adapters, however, junctional complexes themselves can relay extracellular stimuli to the epithelium and initiate cellular responses such as differentiation and apoptosis. In this review, we will highlight recent studies by our group and others which discuss how junctional proteins can promote outside-to-inside signaling and modulate epithelial cell fate. Unraveling the complex crosstalk between epithelial cells and their intercellular junctions is essential to understanding how epithelial barrier function is maintained in vivo and might provide new strategies for the treatment of inflammatory disorders of the intestine.