Delivery of a mucin domain enriched in cysteine residues strengthens the intestinal mucous barrier.
Delivery of a mucin domain enriched in cysteine residues strengthens the intestinal mucous barrier.
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富含半胱氨酸残基的粘蛋白结构域的递送增强了肠粘膜。
DOI：
10.1038/srep09577
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发表时间：
2015-05-14
影响因子：
4.6
通讯作者：
Desseyn JL
中科院分区：
文献类型：
--
作者：
Gouyer V;Dubuquoy L;Robbe-Masselot C;Neut C;Singer E;Plet S;Geboes K;Desreumaux P;Gottrand F;Desseyn JL
肠粘膜屏障的减弱使肠腔内容物进入上皮细胞的机会增加，从而引发炎症反应。在炎症性肠病中，免疫系统处于不适当的持续激活状态，可能是因为肠道粘液对内源性微生物群的保护作用较弱。旨在改善对肠道上皮保护的一般战略仍然缺乏。我们产生了一只转基因小鼠，它将一个由12个连续拷贝的粘蛋白结构域组成的分子分泌到它的肠道粘液中，据信通过建立可逆的相互作用来改变粘液层。我们发现粘液凝胶更坚固，粘蛋白O-糖基化也发生了改变。值得注意的是，转基因小鼠的肠道上皮含有更多有益的乳杆菌。这些修饰与转基因小鼠对化学诱导的结肠炎的易感性降低有关。此外，转基因小鼠对口服的轮状柠檬酸杆菌的清除速度更快，对粘附性侵袭性大肠杆菌灌胃诱导的细菌易位有更好的保护作用。我们的数据显示，将粘蛋白CyS结构域输送到肠腔可以加强在炎症性肠病中受损的肠道粘液层。
A weakening of the gut mucous barrier permits an increase in the access of intestinal luminal contents to the epithelial cells, which will trigger the inflammatory response. In inflammatory bowel diseases, there is an inappropriate and ongoing activation of the immune system, possibly because the intestinal mucus is less protective against the endogenous microflora. General strategies aimed at improving the protection of the intestinal epithelium are still missing. We generated a transgenic mouse that secreted a molecule consisting of 12 consecutive copies of a mucin domain into its intestinal mucus, which is believed to modify the mucus layer by establishing reversible interactions. We showed that the mucus gel was more robust and that mucin O-glycosylation was altered. Notably, the gut epithelium of transgenic mice housed a greater abundance of beneficial Lactobacillus spp. These modifications were associated with a reduced susceptibility of transgenic mice to chemically induced colitis. Furthermore, transgenic mice cleared faster Citrobacter rodentium bacteria which were orally given and mice were more protected against bacterial translocation induced by gavage with adherent–invasive Escherichia coli. Our data show that delivering the mucin CYS domain into the gut lumen strengthens the intestinal mucus blanket which is impaired in inflammatory bowel diseases.
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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
Keystone-Pathogen假设。
DOI：
10.1038/nrmicro2873
发表时间：
2012-10
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
通讯作者：
--
影响因子：
56.9
作者：
Bry, L;Falk, PG;Gordon, JI
通讯作者：
Gordon, JI
影响因子：
3.1
作者：
Borenshtein, Diana;Nambiar, Prashant R.;Schauer, David B.
通讯作者：
Schauer, David B.
影响因子：
4.8
作者：
Desseyn, JL;GuyonnetDuperat, V;Laine, A
通讯作者：
Laine, A