The extent of liver injury determines hepatocyte fate toward senescence or cancer

Cell Death & Disease
Chao WangZhi-Ying He

Abstract

It is well known that induction of hepatocyte senescence could inhibit the development of hepatocellular carcinoma (HCC). Until now, it is still unclear how the degree of liver injury dictates hepatocyte senescence and carcinogenesis. In this study, we investigated whether the severity of injury determines cell fate decisions between hepatocyte senescence and carcinogenesis. After testing of different degrees of liver injury, we found that hepatocyte senescence is strongly induced in the setting of severe acute liver injury. Longer-term, moderate liver injury, on the contrary did not result into hepatocyte senescence, but led to a significant incidence of HCC instead. In addition, carcinogenesis was significantly reduced by the induction of severe acute injury after chronic moderate liver injury. Meanwhile, immune surveillance, especially the activations of macrophages, was activated after re-induction of senescence by severe acute liver injury. We conclude that severe acute liver injury leads to hepatocyte senescence along with activating immune surveillance and a low incidence of HCC, whereas chronic moderate injury allows hepatocytes to proliferate rather than to enter into senescence, and correlates with a high incidence of...Continue Reading

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Citations

Jan 24, 2021·Cellular and Molecular Gastroenterology and Hepatology·Laura Elisa Buitrago-MolinaArndt Vogel
Dec 15, 2020·Mechanisms of Ageing and Development·Melanie EnglerIon Cristian Cirstea
Mar 26, 2021·Seminars in Liver Disease·Sofia Ferreira-GonzalezStuart J Forbes

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Datasets Mentioned

BETA
GSE108328

Methods Mentioned

BETA
PCA
profilers
electrophoresis

Software Mentioned

Statistical Program for Social Sciences software ( SPSS
R package gplots
clusterProfiler R package
GOseq R

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