Hyaluronan 35kDa treatment protects mice from Citrobacter rodentium infection and induces epithelial tight junction protein ZO-1 in vivo.
Hyaluronan 35kDa treatment protects mice from Citrobacter rodentium infection and induces epithelial tight junction protein ZO-1 in vivo.
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DOI：
10.1016/j.matbio.2016.11.001
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发表时间：
2017-10
期刊：
影响因子：
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通讯作者：
de la Motte CA
中科院分区：
文献类型：
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作者：
Kim Y;Kessler SP;Obery DR;Homer CR;McDonald C;de la Motte CA
维持健康的肠道屏障，即肠道微生物群和底层固有层之间的主要物理屏障，对于最佳健康至关重要。上皮完整性对于防止腔内容物（例如细菌及其产物）通过大肠屏障进入至关重要。在这项研究中，我们研究了生物合成的，特定大小的，透明质酸约35 kDa（HA 35）对健康小鼠肠上皮细胞的保护功能，以及小鼠感染啮齿类柠檬酸杆菌，一个建立的模型，模拟感染一种严重的人类病原体，肠致病性E。coli（EPEC）。我们的研究结果表明，用HA 35治疗保护小鼠免受柠檬酸杆菌感染，并增强上皮屏障功能。特别地，我们已经发现HA 35诱导紧密连接蛋白封闭带（ZO）-1在健康和柠檬酸杆菌感染的小鼠中的表达，如通过免疫荧光和蛋白质印迹分析所证明的。此外，我们确定HA 35处理增强ZO-1表达并降低葡聚糖硫酸钠（DSS）诱导的小鼠结肠炎早期阶段的肠通透性。总之，我们的数据表明，HA 35处理增加了紧密连接的表达和功能，这表明了一种保护柠檬酸杆菌感染的新机制。
Maintaining a healthy intestinal barrier, the primary physical barrier between intestinal microbiota and the underlying lamina propria, is critical for optimal health. Epithelial integrity is essential for prevention of the entrance of luminal contents, such as bacteria and their products, through the large intestinal barrier. In this study, we investigated the protective functions of biosynthetic, specific sized, hyaluronan around 35 kDa (HA35) on intestinal epithelium in healthy mice, as well as mice infected Citrobacter rodentium, an established model that mimics infection with a serious human pathogen, enteropathogenic E. coli (EPEC). Our results reveal that treatment with HA35 protects mice from Citrobacter infection and enhances the epithelial barrier function. In particular, we have found that HA35 induces the expression of tight junction protein zonula occludens (ZO)-1 in both healthy and Citrobacter infected mice, as demonstrated by immunoflurorescence and Western blot analyses. Furthermore, we determined that HA35 treatment enhances ZO-1 expression and reduces intestinal permeability at the early stages of dextran sulfate sodium (DSS)-induced colitis in mice. Together, our data demonstrate that the expression and functionality of tight junctions, is increased by HA35 treatment, suggesting a novel mechanism for the protection from Citrobacter infection.