Year: 2019
Type: article
Abstract: of Liverpool had data integrity concerns regarding the mass spectrometry data contributed by Daniel J. Antoine, shown in Figures 3B and 5A of this paper.The authors have also identified errors in the figure labels for Figures 5H and 6D.The authors have provided a corrected version of this article and a description of changes below.In our published work, we reported that hepatocyte-derived HMGB1 links cell death to progenitor responses and hepatocarcinogenesis in chronic liver disease (CLD).We based our conclusions on extensive animal studies, including models of chemically or genetically induced chronic cell death in mice with liver-specific knockouts of HMGB1.While hepatocyte-specific deletion of HMGB1 did not significantly alter hepatic injury levels, inflammation, fibrosis, and regeneration, it reduced hepatocyte metaplasia and ductular/progenitor expansion.Passively released HMGB1 promoted ductular reaction in a nonautonomous fashion through RAGE, but not TLR4 or TLR9, as demonstrated by in vivo studies in mice harboring global receptor knockout and further confirmed by in vitro studies using a bipotential liver progenitor cell line.Mice with liver-specific deletion of HMGB1 displayed reduced HCC development in 3 models of chronic hepatocellular death, but not in a model lacking chronic liver injury, further supporting the role of HMGB1 as a DAMP.Similarly to what we observed for CLD, we found that HMGB1 promoted a progenitor signature within tumors, a key feature of HCC aggressiveness.
DOI: 10.1172/jci128262
Language: English
Subfield: Hepatology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4251449440