Chromogranin A regulates gut permeability via the antagonistic actions of its proteolytic peptides.
Chromogranin A regulates gut permeability via the antagonistic actions of its proteolytic peptides.
复制标题
嗜铬粒蛋白A通过其蛋白水解肽的拮抗作用调节肠道通透性。
DOI：
10.1111/apha.13655
复制
发表时间：
2021-06
期刊：
影响因子：
--
通讯作者：
Mahata SK
中科院分区：
文献类型：
--
作者：
Muntjewerff EM;Tang K;Lutter L;Christoffersson G;Nicolasen MJT;Gao H;Katkar GD;Das S;Ter Beest M;Ying W;Ghosh P;El Aidy S;Oldenburg B;van den Bogaart G;Mahata SK
“渗漏的”肠道屏障与多种疾病的发生和发展有关，例如炎症性肠病（IBD）、肠易激综合征和乳糜泻。在这里，我们展示了由肠内分泌细胞产生的前激素嗜铬粒蛋白A（CgA）和Catestatin（CST：hCgA 352 -372），最丰富的CgA衍生的蛋白水解肽，如何影响肠道屏障。通过免疫组织化学、蛋白质印迹、超微结构和流式细胞术研究分析来自区域特异性CST敲除（CST-KO）小鼠、CgA敲除（CgA-KO）和WT小鼠的结肠组织。FITC-葡聚糖测定用于测量肠屏障功能。向小鼠补充CST或CgA片段胰抑素（PST：CgA 250 -301）。测定盲肠的微生物组成。检测IBD患者血中CgA和CST水平。IBD患者血浆CST水平升高。CST-KO小鼠显示（a）与IBD患者相似的伸长的紧密粘附连接和桥粒，（B）紧密连接蛋白2的表达升高，和（c）肠道炎症。血浆FITC-葡聚糖测量显示CST-KO小鼠的肠旁细胞通透性增加。这与厚壁菌门与拟杆菌门的比例较高有关，这是一种在各种疾病中常见的生态失调模式。用重组CST补充CST-KO小鼠恢复了细胞旁通透性并逆转了炎症，而在CgA-KO小鼠中补充CST和/或PST的CgA-KO小鼠显示肠细胞旁通透性受这两种肽的拮抗作用调节：CST降低通透性，PST增加通透性。前激素CgA调节肠细胞旁通透性。CST是降低渗透性的必要和充分条件，主要通过拮抗PST发挥作用。
A “leaky” gut barrier has been implicated in the initiation and progression of a multitude of diseases, for example, inflammatory bowel disease (IBD), irritable bowel syndrome and celiac disease. Here we show how pro-hormone Chromogranin A (CgA), produced by the enteroendocrine cells, and Catestatin (CST: hCgA352-372), the most abundant CgA-derived proteolytic peptide, affect the gut barrier. Colon tissues from region-specific CST-knockout (CST-KO) mice, CgA-knockout (CgA-KO) and WT mice were analysed by immunohistochemistry, western blot, ultrastructural and flowcytometry studies. FITC-dextran assays were used to measure intestinal barrier function. Mice were supplemented with CST or CgA fragment pancreastatin (PST: CgA250-301). The microbial composition of cecum was determined. CgA and CST levels were measured in blood of IBD patients. Plasma levels of CST were elevated in IBD patients. CST-KO mice displayed (a) elongated tight, adherens junctions and desmosomes similar to IBD patients, (b) elevated expression of Claudin 2, and (c) gut inflammation. Plasma FITC-dextran measurements showed increased intestinal paracellular permeability in the CST-KO mice. This correlated with a higher ratio of Firmicutes to Bacteroidetes, a dysbiotic pattern commonly encountered in various diseases. Supplementation of CST-KO mice with recombinant CST restored paracellular permeability and reversed inflammation, whereas CgA-KO mice supplementation with CST and/or PST in CgA-KO mice showed that intestinal paracellular permeability is regulated by the antagonistic roles of these two peptides: CST reduces and PST increases permeability. The pro-hormone CgA regulates the intestinal paracellular permeability. CST is both necessary and sufficient to reduce permeability and primarily acts by antagonizing PST.
登录
查看更多内容
影响因子：
7.7
作者：
Cani, Patrice D.;Amar, Jacques;Burcelin, Remy
通讯作者：
Burcelin, Remy
影响因子：
5.8
作者：
Eissa, Nour;Hussein, Hayam;Ghia, Jean-Eric
通讯作者：
Ghia, Jean-Eric
DOI：
10.1073/pnas.1219451110
发表时间：
2013-05-28
影响因子：
11.1
作者：
Everard, Amandine;Belzer, Clara;Cani, Patrice D.
通讯作者：
Cani, Patrice D.
循环中儿茶素水平降低与冠状动脉疾病相关：新兴的抗炎作用。
影响因子：
5.3
作者：
Chen, Yanjia;Wang, Xiaoqun;Jin, Wei
通讯作者：
Jin, Wei
影响因子：
5.2
作者：
Bandyopadhyay GK;Mahata SK
通讯作者：
Mahata SK