Functional characterization of the mucus barrier on the Xenopus tropicalis skin surface.
Functional characterization of the mucus barrier on the Xenopus tropicalis skin surface.
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DOI：
10.1073/pnas.1713539115
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发表时间：
2018-01-23
影响因子：
11.1
通讯作者：
Thornton DJ
中科院分区：
文献类型：
--
作者：
Dubaissi E;Rousseau K;Hughes GW;Ridley C;Grencis RK;Roberts IS;Thornton DJ
粘液的产生有助于捕获病原体，防止它们进入体内，同时它还充当许多重要生理事件的界面（例如，气体和养分交换）。在哺乳动物模型中，由于难以进入这些位于内部的组织，对粘液及其组成部分的详细研究受到阻碍。热带爪蟾蝌蚪皮肤提供了一个补充的非哺乳动物模型系统，研究粘膜上皮细胞。利用这一点，我们确定了一种粘蛋白，类似于人类粘蛋白，可以防止感染。该系统提供了一种实验上易于处理的方法来研究粘蛋白和粘液屏障及其在粘膜表面赋予保护的作用。粘液表面代表病原体进入和离开的关键途径。因此，动物已经进化出对抗这些部位感染的策略，特别是产生粘液以防止附着并促进粘液/微生物随后远离下面的上皮表面的运动。使用生物化学，生物物理学和感染的研究，我们已经调查了主机的皮肤粘液屏障的热带爪蟾蝌蚪的保护性能。具体而言，我们已经表征了屏障的主要结构成分，并表明它是一种粘蛋白糖蛋白（Otogelin样或Otogl），具有与人凝胶形成粘蛋白相似的序列、结构域组织和结构特性。这种粘蛋白形成了表面屏障的结构基础（约16 μm厚），通过敲除Otogl而耗尽。重要的是，Otogl敲低导致对机会性病原体嗜水气单胞菌感染的易感性。为了更准确地反映其结构、组织定位和功能，我们将Otogl重命名为Xenopus Skin Mucin或MucXS。我们的研究结果描述了一个可访问和易于处理的模型系统，以定义粘液屏障功能和宿主-微生物相互作用。
The production of mucus helps to trap pathogens, preventing their entry into the body, while it also acts as an interface for many important physiological events (e.g., gas and nutrient exchange). In mammalian models, a detailed study of mucus and its component parts is hindered by the difficulty in accessing these internally located tissues. The Xenopus tropicalis tadpole skin offers a complementary nonmammalian model system to study mucosal epithelia. Using this, we identify a mucin, similar to human mucins, that protects against infection. This system offers an experimentally tractable approach to study mucins and the mucus barrier and their role in conferring protection at mucosal surfaces. Mucosal surfaces represent critical routes for entry and exit of pathogens. As such, animals have evolved strategies to combat infection at these sites, in particular the production of mucus to prevent attachment and to promote subsequent movement of the mucus/microbe away from the underlying epithelial surface. Using biochemical, biophysical, and infection studies, we have investigated the host protective properties of the skin mucus barrier of the Xenopus tropicalis tadpole. Specifically, we have characterized the major structural component of the barrier and shown that it is a mucin glycoprotein (Otogelin-like or Otogl) with similar sequence, domain organization, and structural properties to human gel-forming mucins. This mucin forms the structural basis of a surface barrier (∼6 μm thick), which is depleted through knockdown of Otogl. Crucially, Otogl knockdown leads to susceptibility to infection by the opportunistic pathogen Aeromonas hydrophila. To more accurately reflect its structure, tissue localization, and function, we have renamed Otogl as Xenopus Skin Mucin, or MucXS. Our findings characterize an accessible and tractable model system to define mucus barrier function and host–microbe interactions.
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影响因子：
6.7
作者：
Bergstrom KS;Kissoon-Singh V;Gibson DL;Ma C;Montero M;Sham HP;Ryz N;Huang T;Velcich A;Finlay BB;Chadee K;Vallance BA
通讯作者：
Vallance BA
影响因子：
10.7
作者：
Lang T;Klasson S;Larsson E;Johansson ME;Hansson GC;Samuelsson T
通讯作者：
Samuelsson T
影响因子：
3.2
作者：
Corcoran, Colin P.;Cameron, Andrew D. S.;Dorman, Charles J.
通讯作者：
Dorman, Charles J.
影响因子：
4.4
作者：
Lang T;Hansson GC;Samuelsson T
通讯作者：
Samuelsson T
影响因子：
4.4
作者：
Cao, Rui;Wang, T. Tiffany;Kesimer, Mehmet
通讯作者：
Kesimer, Mehmet