Up-regulation of miR-155 contributes to TNF-mediated hepatocyte apoptosis in acute liver failure

Özet

Background/Aims: Acute liver failure (ALF) is due to severe immune response, resulting in massive apoptosis/necrosis of hepatocytes.The precise mechanism has not been explored yet.Materials and Methods: The mouse with ALF model was induced by D-GalN/LPS; the hepatic miRNAs expression profile was evaluated by miRNA microarray and verified by RT-PCR. During the ALF in mice, the miR-155 expression was detected in the liver as wellas in spleen. Then the correlation between miR-155 and inflammatory cytokines was evaluated. Furthermore, the miR-155 expressionin activated Raw264.7 cells and apoptotic hepatocytes was also studied. Finally, the regulatory roles of miR-155 in TNF expression ofapoptotic hepatocytes were shown.Results: It was shown that miRNAs changed in the mice with ALF relating to hepatocytes apoptosis/necrosis; the selected miRNAswere confirmed with RT-PCR. miR-155 was up-regulated, but miR-698, -720, and -329 were down-regulated. Moreover, hepatic miR155 was up-regulated at all-time points in the liver, but only at 7 h in spleen of mice with ALF. A significant correlation was observedbetween hepatic miR-155 and TNF/IL-6 in mice with ALF, which was supported by the findings in vitro showing up-regulated miR-155in Raw264.7 cells and Hepa1-6 cells under LPS or D-GalN+TNF induction, respectively. Moreover, a correlation was observed betweenmiR155 and TNF levels in vivo and in vitro.Conclusion: These data demonstrate that miR-155 regulates TNF-mediated hepatocyte apoptosis in ALF, which provides some usefulinformation in both basic and clinical researches.