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Oval cells compensate for damage and replicative senescence of mature hepatocytes in mice with fatty liver disease.

Publication ,  Journal Article
Yang, S; Koteish, A; Lin, H; Huang, J; Roskams, T; Dawson, V; Diehl, AM
Published in: Hepatology
February 2004

Hepatic steatosis may have a generally benign prognosis, either because most hepatocytes are not significantly injured or mechanisms to replace damaged hepatocytes are induced. To determine the relative importance of these mechanisms, we compared hepatocyte damage and replication in ethanol-fed and ob/ob mice with very indolent fatty liver disease to that of healthy control mice and PARP-1(-/-) mice with targeted disruption of the DNA repair enzyme, poly(ADP-ribose) polymerase. Compared to the healthy controls, both groups with fatty livers had significantly higher serum alanine aminotransferase values, hepatic mitochondrial H(2)O(2) production, and hepatocyte oxidative DNA damage. A significantly smaller proportion of the hepatocytes from fatty livers entered S phase when cultured with mitogens. Moreover, this replicative senescence was not reversed by treating cultured hepatocytes with agents (i.e., betaine or leptin) that improve liver disease in intact ethanol-fed or leptin-deficient mice. Hepatocytes from PARP1(-/-) mice also had more DNA damage and reduced DNA synthesis in response to mitogens. However, neither mice with fatty livers nor PARP-1-deficient mice had atrophic livers. All of the mice with senescent mature hepatocytes exhibited hepatic accumulation of liver progenitor (oval) cells and oval cell numbers increased with the demand for hepatocyte replacement. Therefore, although hepatic oxidant production and damage are generally increased in fatty livers, expansion of hepatic progenitor cell populations helps to compensate for the increased turnover of damaged mature hepatocytes. In conclusion, these results demonstrate that induction of mechanisms to replace damaged hepatocytes is important for limiting the progression of fatty liver disease.

Duke Scholars

Published In

Hepatology

DOI

ISSN

0270-9139

Publication Date

February 2004

Volume

39

Issue

2

Start / End Page

403 / 411

Location

United States

Related Subject Headings

  • Stem Cells
  • Poly(ADP-ribose) Polymerases
  • Oxidative Stress
  • Mice, Obese
  • Mice, Mutant Strains
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Lipotropic Agents
  • Leptin
 

Citation

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ICMJE
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Yang, S., Koteish, A., Lin, H., Huang, J., Roskams, T., Dawson, V., & Diehl, A. M. (2004). Oval cells compensate for damage and replicative senescence of mature hepatocytes in mice with fatty liver disease. Hepatology, 39(2), 403–411. https://doi.org/10.1002/hep.20082
Yang, Shiqi, Ayman Koteish, Huizhi Lin, Jiawen Huang, Tania Roskams, Valina Dawson, and Anna Mae Diehl. “Oval cells compensate for damage and replicative senescence of mature hepatocytes in mice with fatty liver disease.Hepatology 39, no. 2 (February 2004): 403–11. https://doi.org/10.1002/hep.20082.
Yang S, Koteish A, Lin H, Huang J, Roskams T, Dawson V, et al. Oval cells compensate for damage and replicative senescence of mature hepatocytes in mice with fatty liver disease. Hepatology. 2004 Feb;39(2):403–11.
Yang, Shiqi, et al. “Oval cells compensate for damage and replicative senescence of mature hepatocytes in mice with fatty liver disease.Hepatology, vol. 39, no. 2, Feb. 2004, pp. 403–11. Pubmed, doi:10.1002/hep.20082.
Yang S, Koteish A, Lin H, Huang J, Roskams T, Dawson V, Diehl AM. Oval cells compensate for damage and replicative senescence of mature hepatocytes in mice with fatty liver disease. Hepatology. 2004 Feb;39(2):403–411.
Journal cover image

Published In

Hepatology

DOI

ISSN

0270-9139

Publication Date

February 2004

Volume

39

Issue

2

Start / End Page

403 / 411

Location

United States

Related Subject Headings

  • Stem Cells
  • Poly(ADP-ribose) Polymerases
  • Oxidative Stress
  • Mice, Obese
  • Mice, Mutant Strains
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Lipotropic Agents
  • Leptin