Author/Authors :
Dapito، نويسنده , , Dianne H. and Mencin، نويسنده , , Ali and Gwak، نويسنده , , Geum-Youn and Pradere، نويسنده , , Jean-Philippe and Jang، نويسنده , , Myoung-Kuk and Mederacke، نويسنده , , Ingmar and Caviglia، نويسنده , , Jorge M. and Khiabanian، نويسنده , , Hossein and Adeyemi، نويسنده , , Adebowale and Bataller، نويسنده , , Ramon and Lefkowitch، نويسنده , , Jay H. and Bower، نويسنده , , Maureen and Friedman، نويسنده , , Richard and Sartor، نويسنده , , R. Balfour and Rabadan، نويسنده , , Raul and Schwabe، نويسنده , , Robert F.، نويسنده ,
Abstract :
Summary
sed 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.
