Desmosomes are the least understood intercellular junctions in the intestinal epithelia and provide cell-cell adhesion via the cadherins desmoglein (Dsg)2 and desmocollin (Dsc)2. We studied these cadherins in Crohn's disease (CD) patients and in newly generated conditional villin-Cre DSG2 and DSC2 knockout mice (DSG2^ΔIEC; DSC2^ΔIEC). CD patients exhibited altered desmosomes and reduced Dsg2/Dsc2 levels. The intestines of both transgenic animal lines were histopathologically inconspicuous. However, DSG2^ΔIEC, but not DSC2^ΔIEC mice displayed an increased intestinal permeability, a wider desmosomal space as well as alterations in desmosomal and tight junction components. After dextran sodium sulfate (DSS) treatment and Citrobacter rodentium exposure, DSG2^ΔIEC mice developed a more-pronounced colitis, an enhanced intestinal epithelial barrier disruption, leading to a stronger inflammation and activation of epithelial pSTAT3 signaling. No susceptibility to DSS-induced intestinal injury was noted in DSC2^ΔIEC animals. Dsg2 interacted with the cytoprotective chaperone Hsp70. Accordingly, DSG2^ΔIEC mice had lower Hsp70 levels in the plasma membrane compartment, whereas DSC2^ΔIEC mice displayed a compensatory recruitment of galectin 3, a junction-tightening protein. Our results demonstrate that Dsg2, but not Dsc2 is required for the integrity of the intestinal epithelial barrier in vivo.

中文翻译：

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桥粒芯糖蛋白 2，而非桥粒芯糖蛋白 2，可保护肠上皮细胞免受损伤。

桥粒是肠上皮细胞中了解最少的细胞间连接，它通过钙粘蛋白桥粒芯糖蛋白 (Dsg)2 和桥粒芯胶蛋白 (Dsc)2 提供细胞间粘附。我们在克罗恩病 (CD) 患者和新生成的条件性 villin-Cre DSG2 和 DSC2 敲除小鼠（DSG2 ^ΔIEC；DSC2 ^ΔIEC）中研究了这些钙粘蛋白。CD 患者表现出改变的桥粒和降低的 Dsg2/Dsc2 水平。两种转基因动物系的肠在组织病理学上都不显眼。然而，DSG2 ^ΔIEC，而不是 DSC2 ^ΔIEC小鼠表现出肠道通透性增加、桥粒间隙变宽以及桥粒和紧密连接成分发生变化。在葡聚糖硫酸钠 (DSS) 处理和柠檬酸杆菌啮齿类动物暴露后，DSG2 ^ΔIEC小鼠发生了更明显的结肠炎，肠上皮屏障破坏增强，导致更强烈的炎症和上皮 pSTAT3 信号传导激活。^{在 DSC2 ΔIEC}动物中没有发现对 DSS 诱导的肠损伤的易感性。Dsg2 与细胞保护伴侣 Hsp70 相互作用。因此，DSG2 ^ΔIEC小鼠质膜隔室中的 Hsp70 水平较低，而 DSC2 ^ΔIEC小鼠表现出半乳糖凝集素 3 的代偿性募集，半乳糖凝集素 3 是一种连接紧缩蛋白。我们的结果表明，体内肠上皮屏障的完整性需要 Dsg2 而不是 Dsc2。