Aggravated gut inflammation in mice lacking the taste signaling protein α-gustducin.
Aggravated gut inflammation in mice lacking the taste signaling protein α-gustducin.
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缺乏味觉信号蛋白α-味导素的小鼠肠道炎症加剧
DOI：
10.1016/j.bbi.2018.04.010
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发表时间：
2018-07
期刊：
影响因子：
--
通讯作者：
Wang H
中科院分区：
文献类型：
--
作者：
Feng P;Chai J;Yi H;Redding K;Margolskee RF;Huang L;Wang H
炎症性肠病(IBD)是一种与免疫相关的衰弱疾病，影响着超过140万美国人。最近的研究表明，味觉受体信号远不止参与感知食物的味道，而且味觉受体已经定位于各种口腔外组织中。新发现的味觉受体和下游信号蛋白的功能之一是调节对微生物和寄生虫的免疫反应。我们先前发现味觉受体信号通路的组成部分在肠上皮细胞亚群中表达。α-Gustducin是一个关键的G蛋白α亚基，参与甜味、鲜味和苦味受体信号的传递，在肠粘膜中表达。在本研究中，我们利用葡聚糖硫酸钠诱导的肠易激综合征模型，利用α-Gustducin基因敲除小鼠，研究了α-Gustducin在肠黏膜免疫和炎症调节中的作用。DSS是一种化学致病原，可导致肠道上皮损伤和炎症。我们分析了α-Gustducin基因敲除小鼠和野生型对照小鼠在饮水中给予DSS后所致的结肠炎。我们的结果表明，在实验期间，与野生型小鼠相比，基因敲除小鼠体重减轻、腹泻、肠道出血和炎症加重，同时伴随着免疫细胞浸润的增加，结肠中肿瘤坏死因子和干扰素-γ的表达增加，而IL-13和IL-5的表达减少。这些结果表明，味觉受体信号通路可能在调节肠道免疫平衡和炎症中发挥关键作用。
Inflammatory bowel disease (IBD) is a debilitating immune-related condition that affects over 1.4 million Americans. Recent studies indicate that taste receptor signaling is involved in much more than sensing food flavor, and taste receptors have been localized in a variety of extra-oral tissues. One of the newly revealed functions of taste receptors and downstream signaling proteins is modulation of immune responses to microbes and parasites. We previously found that components of the taste receptor signaling pathway are expressed in subsets of the intestinal epithelial cells. α-Gustducin, a key G-protein α subunit involved in sweet, umami, and bitter taste receptor signaling, is expressed in the intestinal mucosa. In this study, we investigated the role of α-gustducin in regulation of gut mucosal immunity and inflammation using α-gustducin knockout mice in the dextran sulfate sodium (DSS)-induced IBD model. DSS is a chemical colitogen that can cause intestinal epithelial damage and inflammation. We analyzed DSS-induced colitis in α-gustducin knockout versus wild-type control mice after administration of DSS in drinking water. Our results show that the knockout mice had aggravated weight loss, diarrhea, intestinal bleeding, and inflammation over the experimental period compared to wild-type mice, concurrent with augmented immune cell infiltration and increased expression of TNF and IFN-γ but decreased expression of IL-13 and IL-5 in the colon. These results suggest that the taste receptor signaling pathway may play critical roles in regulating gut immune balance and inflammation.
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影响因子：
5.3
作者：
Feng, Pu;Chai, Jinghua;Wang, Hong
通讯作者：
Wang, Hong
影响因子：
15.9
作者：
Lee, Robert J.;Xiong, Guoxiang;Cohen, Noam A.
通讯作者：
Cohen, Noam A.
影响因子：
2.5
作者：
Bezencon, C.;Fuerholz, A.;Damak, S.
通讯作者：
Damak, S.
影响因子：
64.8
作者：
Wong, GT;Gannon, KS;Margolskee, RF
通讯作者：
Margolskee, RF
簇细胞，味觉化学细胞，在肠道中编排寄生虫2型免疫力。
DOI：
10.1126/science.aaf1648
发表时间：
2016-03-18
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Howitt MR;Lavoie S;Michaud M;Blum AM;Tran SV;Weinstock JV;Gallini CA;Redding K;Margolskee RF;Osborne LC;Artis D;Garrett WS
通讯作者：
Garrett WS