The mystery of liver regeneration

Court, Fiona; Wemyss‐Holden, Simon A.; Dennison, Ashley R.; Maddern, Guy J.

doi:10.1046/j.1365-2168.2002.02166.x

Cited by 121 publications

(96 citation statements)

References 44 publications

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“…There is roughly 10 times more CuZnSOD and 10 to 20 times more catalase activity in the liver than in the heart, lung, skeletal muscle, and brain ( TT Huang, unpublished data). Liver also has a tremendous capacity for regeneration, and can grow back to its original size with as much as 70% of the mass removed (Court et al, 2002;Diehl, 2002;Zimmermann, 2002). It is likely that high-level ROS generation makes liver susceptible to perturbations in antioxidant levels, and the high capacity for regeneration provides the opportunity to select for cells with replication advantage for clonal expansion.…”

Section: Discussionmentioning

confidence: 99%

CuZnSOD deficiency leads to persistent and widespread oxidative damage and hepatocarcinogenesis later in life

et al. 2004

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Mice deficient in CuZn superoxide dismutase (CuZn-SOD) showed no overt abnormalities during development and early adulthood, but had a reduced lifespan and increased incidence of neoplastic changes in the liver. Greater than 70% of Sod1À/À mice developed liver nodules that were either nodular hyperplasia or hepatocellular carcinoma (HCC). Cross-sectional studies with livers collected from Sod1À/À and age-matched þ / þ controls revealed extensive oxidative damage in the cytoplasm and, to a lesser extent, in the nucleus and mitochondria from as early as 3 months of age. A marked reduction in cytosolic aconitase, increased levels of 8-oxo dG and F2-isoprostanes, and a moderate reduction in glutathione peroxidase activities and porin levels were observed in all age groups of Sod1À/À mice examined. There were also age-related reductions in Mn superoxide dismutase activities and carbonic anhydrase III. Parallel to the biochemical changes, there were progressive increases in the DNA repair enzyme APEX1, the cell cycle control proteins cyclin D1 and D3, and the hepatocyte growth factor receptor Met. Increased cell proliferation in the presence of persistent oxidative damage to macromolecules likely contributes to hepatocarcinogenesis later in life.

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Section: Discussionmentioning

confidence: 99%

CuZnSOD deficiency leads to persistent and widespread oxidative damage and hepatocarcinogenesis later in life

et al. 2004

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“…The liver is a unique organ in that regeneration occurs by DNA replication and mitosis, whereas most other organs simply hypertrophy (1). Stimulators of hepatic regeneration include hepatocyte (HGF) and epidermal growth factor (EGF), transforming growth factor-α (TGF-α), and the potent stimulators of angiogenesis, fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF) (2).…”

Section: Introductionmentioning

confidence: 99%

A Critical Role for Matrix Metalloproteinases in Liver Regeneration

Alwayn

Verbesey

Kim

et al. 2008

Journal of Surgical Research

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“…[1][2][3] Although various genetic and biological factors that play a role in this phenomenon have been extensively investigated, [4][5][6][7][8] the mechanisms responsible for the initiation, maintenance, and suspension of hepatocyte proliferation have not been fully elucidated. Two aspects of liver regeneration that appear to be important are (1) strong inhibition of the cytotoxic activity of liver-resident natural killer (NK) cells, which becomes evident within a few hours after partial hepatectomy (PH) and terminates at the end of the regenerative process 9,10 ; and (2) a significant increase in circulating estrogen level and expression of estrogen receptors in tissue, regardless of gender or species.…”

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confidence: 99%