Promotion of hepatocellular carcinoma by the intestinal microbiota and TLR4.
Promotion of hepatocellular carcinoma by the intestinal microbiota and TLR4.
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DOI：
10.1016/j.ccr.2012.02.007
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发表时间：
2012-04-17
期刊：
影响因子：
50.3
通讯作者：
Schwabe RF
中科院分区：
文献类型：
--
作者：
Dapito DH;Mencin A;Gwak GY;Pradere JP;Jang MK;Mederacke I;Caviglia JM;Khiabanian H;Adeyemi A;Bataller R;Lefkowitch JH;Bower M;Friedman R;Sartor RB;Rabadan R;Schwabe RF
肠道细菌移位增加是慢性肝病的一个标志，并导致肝脏炎症和纤维化。在这里，我们测试了肠道微生物区系和Toll样受体(TLRs)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后果。慢性损伤肝脏的肝癌发生依赖于肠道微生物区系，以及非骨髓来源的常驻肝细胞中TLR4的激活。TLR4和肠道微生物区系不是启动肝细胞癌所必需的，而是促进肝细胞癌、介导增殖增加、表达肝分裂原表型调节素和防止细胞凋亡所必需的。肠道绝育仅限于肝癌发生的晚期，减少了肝癌的发生，这表明肠道微生物区系和TLR4是晚期肝病中预防肝癌的治疗靶点。
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 microbiota and TLR4 represent therapeutic targets for HCC prevention in advanced liver disease.
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影响因子：
50.3
作者：
Luedde, Tom;Beraza, Naiara;Pasparakis, Manolis
通讯作者：
Pasparakis, Manolis
影响因子：
29.4
作者：
Dolganiuc, Angela;Norkina, Oxana;Szabo, Gyongyi
通讯作者：
Szabo, Gyongyi
影响因子：
50.3
作者：
Haybaeck J;Zeller N;Wolf MJ;Weber A;Wagner U;Kurrer MO;Bremer J;Iezzi G;Graf R;Clavien PA;Thimme R;Blum H;Nedospasov SA;Zatloukal K;Ramzan M;Ciesek S;Pietschmann T;Marche PN;Karin M;Kopf M;Browning JL;Aguzzi A;Heikenwalder M
通讯作者：
Heikenwalder M
DOI：
10.1056/nejmoa0804525
发表时间：
2008-11-06
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hoshida Y;Villanueva A;Kobayashi M;Peix J;Chiang DY;Camargo A;Gupta S;Moore J;Wrobel MJ;Lerner J;Reich M;Chan JA;Glickman JN;Ikeda K;Hashimoto M;Watanabe G;Daidone MG;Roayaie S;Schwartz M;Thung S;Salvesen HB;Gabriel S;Mazzaferro V;Bruix J;Friedman SL;Kumada H;Llovet JM;Golub TR
通讯作者：
Golub TR
影响因子：
50.3
作者：
Bruix, J;Boix, L;Llovet, JM
通讯作者：
Llovet, JM