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- W2790482497 abstract "Cell death is a key driver of disease progression and carcinogenesis in chronic liver disease (CLD), highlighted by the well-established clinical correlation between hepatocellular death and risk for the development of cirrhosis and hepatocellular carcinoma (HCC). Moreover, hepatocellular death is sufficient to trigger fibrosis and HCC in mice. However, the pathways through which cell death drives CLD progression remain elusive. Here, we tested the hypothesis that high-mobility group box 1 (HMGB1), a damage-associated molecular pattern (DAMP) with key roles in acute liver injury, may link cell death to injury responses and hepatocarcinogenesis in CLD. While liver-specific HMGB1 deficiency did not significantly affect chronic injury responses such as fibrosis, regeneration, and inflammation, it inhibited ductular/progenitor cell expansion and hepatocyte metaplasia. HMGB1 promoted ductular expansion independently of active secretion in a nonautonomous fashion, consistent with its role as a DAMP. Liver-specific HMGB1 deficiency reduced HCC development in 3 mouse models of chronic injury but not in a model lacking chronic liver injury. As with CLD, HMGB1 ablation reduced the expression of progenitor and oncofetal markers, a key determinant of HCC aggressiveness, in tumors. In summary, HMGB1 links hepatocyte death to ductular reaction, progenitor signature, and hepatocarcinogenesis in CLD." @default.
- W2790482497 created "2018-03-29" @default.
- W2790482497 creator A5033308270 @default.
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- W2790482497 creator A5073738784 @default.
- W2790482497 creator A5078154370 @default.
- W2790482497 date "2018-05-07" @default.
- W2790482497 modified "2023-10-16" @default.
- W2790482497 title "HMGB1 links chronic liver injury to progenitor responses and hepatocarcinogenesis" @default.
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- W2790482497 doi "https://doi.org/10.1172/jci91786" @default.
- W2790482497 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6436874" @default.
- W2790482497 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30932913" @default.
- W2790482497 hasPublicationYear "2018" @default.
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