Silence Please!: siRNA approaches to tighten the intestinal barrier in vivo.
Silence Please!: siRNA approaches to tighten the intestinal barrier in vivo.
复制标题
请保持沉默！：siRNA 方法可收紧体内肠道屏障。
DOI：
10.1016/j.ajpath.2013.10.001
复制
发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Pothoulakis,Charalabos
中科院分区：
文献类型：
--
作者：
Bakirtzi,Kyriaki;Hoffman,JillM;Pothoulakis,Charalabos
肠上皮的动态特性对其在肠道内稳态和人类疾病中的作用至关重要。虽然肠上皮通常被称为粘膜或肠屏障，因为它能够限制管腔内的有害分子或抗原进入体内，但它也允许对正常肠道功能至关重要的液体、离子和营养物质的细胞旁运输。促进肠上皮通透性的粘膜屏障的一个关键结构成分是细胞内紧密连接，紧密连接屏障的缺陷与慢性肠道炎症的病因有关。在这一期的《美国病理学杂志》上，al - sadi等报道了促炎细胞因子肿瘤坏死因子-α (TNF-α)介导的肠紧密连接通透性增加的分子机制和细胞内通路。肠通透性增加与炎症性肠病（IBD）发病机制有关的假说最早由Shorter等人在20世纪70年代初提出。尽管随后有几项研究显示克罗恩病患者的肠屏障功能下降与肠屏障功能下降有关，但Hollander等人首次证明克罗恩病患者及其健康亲属的肠道通透性存在原发性缺陷。其他研究小组扩展了这些发现，并提供了在克罗恩病患者一级亲属中观察到的肠通透性增加的遗传联系（NOD2 3020insC）。7,8,9总的来说，这些研究支持这样一个概念，即肠道通透性增加可能通过增加腔内抗原的转运而使人易患慢性肠道炎症。
The dynamic nature of the intestinal epithelium is central to its roles in both intestinal homeostasis and human disease. Although often referred to as the mucosal or intestinal barrier for its ability to limit harmful molecules or antigens in the lumen from entering the body, the intestinal epithelium also allows for paracellular transport of fluid, ions, and nutrients that are crucial for normal gut function. A key structural component of the mucosal barrier that contributes to intestinal epithelial permeability is the intracellular tight junction, and defects in the tight junction barrier have been implicated in the etiology of chronic intestinal inflammation. In this issue of The American Journal of Pathology, Al-Sadi et al 1 report on the molecular mechanisms and intracellular pathways involved in increased intestinal tight junction permeability mediated by the pro-inflammatory cytokine, tumor necrosis factor-α (TNF-α).The hypothesis that increased intestinal permeability contributes to the pathogenesis of inflammatory bowel disease (IBD) was first described by Shorter et al 2 in the early 1970s. Although several studies followed showing an association with decreased barrier function in patients with Crohn’s disease, 3, 4, 5 it was Hollander et al 6 who first demonstrated that both Crohn’s disease patients and a subset of their healthy relatives have a primary defect in intestinal permeability. Other groups expanded these findings and provided a genetic link (NOD2 3020insC) for the increased intestinal permeability observed in first-degree relatives of patients with Crohn’s disease. 7, 8, 9 Collectively, these studies support the concept that increased intestinal permeability may predispose one to develop chronic intestinal inflammation through increased transport of luminal antigens.