Deficiency of intestinal mucin-2 ameliorates experimental alcoholic liver disease in mice.
Deficiency of intestinal mucin-2 ameliorates experimental alcoholic liver disease in mice.
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肠粘膜-2的缺乏可改善小鼠的实验性酒精性肝病。
DOI：
10.1002/hep.26321
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发表时间：
2013-07
期刊：
影响因子：
13.5
通讯作者：
Schnabl, Bernd
中科院分区：
文献类型：
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作者：
Hartmann, Phillipp;Chen, Peng;Wang, Hui J.;Wang, Lirui;McCole, Declan F.;Brandl, Katharina;Starkel, Peter;Belzer, Clara;Hellerbrand, Claus;Tsukamoto, Hidekazu;Ho, Samuel B.;Schnabl, Bernd
肠粘液层保护上皮免受胃肠道中存在的有害物质、病毒和病原菌的侵害。它由粘蛋白组成，主要是粘蛋白-2（Muc 2），由肠的杯状细胞分泌。实验性酒精性肝病需要细菌产物穿过肠屏障进入体循环，这在肝脏中诱导炎症反应并促成脂肪性肝炎。我们研究了肠粘液层，特别是Muc 2在小鼠实验性酒精相关性肝病发展中的作用。我们研究了实验性酒精诱导的肝病，通过Tsukamoto-French方法（包括连续胃内喂养等热量饮食或酒精）在野生型和Muc 2 −/−小鼠中诱导。Muc 2 −/−小鼠表现出较少的酒精诱导的肝损伤和脂肪变性，而在野生型小鼠中发展。最值得注意的是，Muc 2 −/−小鼠在酒精喂养后血浆脂多糖水平显著低于野生型小鼠。与野生型小鼠相比，Muc 2 −/−小鼠受到保护，免受依赖于肠粘蛋白的酒精相关微生物组变化的影响。与野生型小鼠相比，在喂食等热量饮食或酒精的Muc 2 −/−小鼠的空肠中，抗微生物蛋白Reg 3b和Reg 3g的表达水平显著更高。因此，Muc 2 −/−小鼠表现出对肠道细菌的杀伤作用增加，并防止肠道细菌过度生长。结论：Muc 2 −/−小鼠在酒精喂养时可免受肠道细菌过度生长和生态失调的影响。随后，较少量的细菌产物如内毒素转移到体循环中，减少肝脏疾病。
The intestinal mucus layer protects the epithelium from noxious agents, viruses, and pathogenic bacteria present in the gastrointestinal tract. It is composed of mucins, predominantly mucin-2 (Muc2), secreted by goblet cells of the intestine. Experimental alcoholic liver disease requires translocation of bacterial products across the intestinal barrier into the systemic circulation, which induces an inflammatory response in the liver and contributes to steatohepatitis. We investigated the roles of the intestinal mucus layer, and in particular Muc2, in development of experimental alcohol-associated liver disease in mice. We studied experimental alcohol-induced liver disease, induced by the Tsukamoto-French method (which involves continuous intragastric feeding of an isocaloric diet or alcohol) in wild-type and Muc2−/− mice. Muc2−/− mice showed less alcohol-induced liver injury and steatosis that developed in wild-type mice. Most notably, Muc2−/− mice had significantly lower plasma levels of lipopolysaccharide than wild-type mice after alcohol feeding. In contrast to wild-type mice, Muc2−/− mice were protected from alcohol-associated microbiome changes that are dependent on intestinal mucins. The anti-microbial proteins Reg3b and Reg3g were expressed at significantly higher levels in the jejunum of Muc2−/− mice fed the isocaloric diet or alcohol, compared with wild-type mice. Consequently, Muc2−/− mice showed increased killing of commensal bacteria and prevented intestinal bacterial overgrowth. Conclusion: Muc2−/− mice are protected from intestinal bacterial overgrowth and dysbiosis in response to alcohol feeding. Subsequently, lower amounts of bacterial products such as endotoxin translocate into the systemic circulation, decreasing liver disease.
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影响因子：
64.8
作者：
Brandl, Katharina;Plitas, George;Mihu, Coralia N.;Ubeda, Carles;Jia, Ting;Fleisher, Martin;Schnabl, Bernd;DeMatteo, Ronald P.;Pamer, Eric G.
通讯作者：
Pamer, Eric G.
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
DOI：
10.1016/j.alcohol.2008.12.009
发表时间：
2009-03
期刊：
Alcohol (Fayetteville, N.Y.)
影响因子：
--
作者：
Forsyth CB;Farhadi A;Jakate SM;Tang Y;Shaikh M;Keshavarzian A
通讯作者：
Keshavarzian A
DOI：
10.4081/ejh.2010.e49
发表时间：
2010-11-26
期刊：
European journal of histochemistry : EJH
影响因子：
--
作者：
Lacunza E;Ferretti V;Barbeito C;Segal-Eiras A;Croce MV
通讯作者：
Croce MV
DOI：
10.1002/hep.22470
发表时间：
2008-10
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
Hritz I;Mandrekar P;Velayudham A;Catalano D;Dolganiuc A;Kodys K;Kurt-Jones E;Szabo G
通讯作者：
Szabo G