Targeting gut flora to prevent progression of hepatocellular carcinoma
Targeting gut flora to prevent progression of hepatocellular carcinoma
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DOI：
10.1016/j.jhep.2012.08.019
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发表时间：
2013-02-01
影响因子：
25.7
通讯作者：
Moniaux, Nicolas
中科院分区：
文献类型：
--
作者：
Darnaud, Marion;Faivre, Jamila;Moniaux, Nicolas
肠道细菌移位增加是慢性肝病的标志，并导致肝脏炎症和纤维化。在这里，我们测试了肠道微生物群和Toll样受体（TLR）促进肝细胞癌（HCC）的假设，肝细胞癌是慢性肝损伤、炎症和纤维化的长期结果。慢性损伤肝脏的肝癌发生依赖于肠道微生物群和非骨髓来源的常驻肝细胞中的TLR4活化。TLR4和肠道微生物群不是HCC启动所需的，而是HCC促进所需的，介导增殖增加，肝促分裂原epiregulin的表达和细胞凋亡的预防。局限于肝癌发生晚期的肠道灭菌减少了HCC，这表明肠道微生物群和TLR4代表了晚期肝病中HCC预防的治疗靶点。(C)2012年欧洲肝脏研究协会。Elsevier B.V.出版，保留所有权利。
Increased translocation of intestinal bacteria is a hallmark of chronic liver disease and contributes to hepatic inflammation and fibrosis. Here we tested the hypothesis that the intestinal microbiota and Toll-like receptors (TLRs) promote hepatocellular carcinoma (HCC), a long-term consequence of chronic liver injury, inflammation, and fibrosis. Hepatocarcinogenesis in chronically injured livers depended on the intestinal microbiota and TLR4 activation in non-bone-marrow-derived resident liver cells. TLR4 and the intestinal microbiota were not required for HCC initiation but for HCC promotion, mediating increased proliferation, expression of the hepatomitogen epiregulin, and prevention of apoptosis. Gut sterilization restricted to late stages of hepatocarcinogenesis reduced HCC, suggesting that the intestinal micro biota and TLR4 represent therapeutic targets for HCC prevention in advanced liver disease. (C) 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.