Disease relevance of Liver Regeneration

• TGF beta 1 may have an important role in the pathogenesis of fibrosis in patients with chronic liver disease, and TGF alpha expression may be associated with liver regeneration in these patients [1].
• Antioxidant treatment also prevents TNFalpha-mediated fulminant liver failure without affecting liver regeneration [2].
• In a liver regeneration model that requires TNF signaling, Timp3(-/-) mice succumbed to liver failure [3].
• Changes in heparin-binding fibroblast growth factor gene expression and receptor phenotype occur during liver regeneration and in hepatoma cells [4].
• Immunotherapy directed against alpha-fetoprotein results in autoimmune liver disease during liver regeneration in mice [5].

Psychiatry related information on Liver Regeneration

• However, cytokine defense mechanisms are intact during noncomplicated liver regeneration, as indicated by normal TNF-alpha and IL-6 responses to endotoxemia or sepsis [6].

High impact information on Liver Regeneration

• Abnormal TNF activity in Timp3-/- mice leads to chronic hepatic inflammation and failure of liver regeneration [3].
• Mice with targeted disruption of the interleukin-6 (IL-6) gene had impaired liver regeneration characterized by liver necrosis and failure [7].
• Hepatocyte growth factor (HGF) is a plasminogen-like protein thought to be a humoral mediator of liver regeneration [8].
• The postnatal repression of transcription of the AFP gene in both liver and gut, as well as the reinitiation of its transcription during liver regeneration, is mimicked by the introduced gene when it is linked to the enhancer domains together or singly [9].
• The proinflammatory mediators C3a and C5a are essential for liver regeneration [10].

Chemical compound and disease context of Liver Regeneration

• LTB4 stagnates in the liver with obstructive jaundice, because LTB4 is excreted in the bile; therefore, LTB4 may have an effect on liver regeneration after hepatectomy with obstructive jaundice [11].
• In the western world, ethanol is the single most important aetiological factor associated with liver disease, and it appears crucial to determine if ethanol interferes with liver regeneration [12].
• CONCLUSION: Selective plasma filtration improved survival time and expedited liver regeneration in pigs with fulminant hepatic failure [13].
• In a mouse model of acute liver failure induced by d-galactosamine administration, a single low dose of a hyper-IL-6-encoding adenoviral vector, in contrast to an adeno-IL-6 vector, maintained liver function, prevented the progression of liver necrosis, and induced liver regeneration, leading to dramatically enhanced survival [14].
• CONCLUSIONS: Glutathione depletion and hypothyroidism affect the mitochondrial function during liver regeneration [15].

Biological context of Liver Regeneration

• To test this hypothesis, the steady-state messenger RNA levels of several protooncogenes involved in cellular proliferation were measured in livers obtained from ethanol-fed rats and isocalorically maintained controls before and during surgically-induced liver regeneration [16].
• For induction of liver regeneration, partial hepatectomy was performed and mice were monitored by serial histopathologic examinations and measurements of serum ALT activities (U/L), and by determination of the kinetics of AFP-specific T-cell responses [5].
• CONCLUSIONS: Abundant phosphocreatine promotes liver regeneration by reinforced hepatic energy metabolism [17].
• Impaired liver regeneration is accompanied by compensatory physiological responses that include prolonged up-regulation of HGF/SF and IL-6 in peripheral blood [18].
• Alteration of epidermal growth factor-dependent phosphorylation during rat liver regeneration [19].

Anatomical context of Liver Regeneration

• The potential role of epidermal growth factor (EGF) in the regulation of rat liver regeneration was examined by assessing the binding of 125I-EGF to hepatic membranes isolated at various times after partial hepatectomy [20].
• Adoptive transfer of IFN-gamma +/+ NK cells, but not IFN-gamma -/- NK cells, restores the ability of polyI:C to attenuate liver regeneration in NK-depleted mice [21].
• METHODS: To determine how endothelial progenitor cells participate in liver regeneration, human or mouse endothelial progenitor cells were transplanted into the mice with carbon tetrachloride-induced acute liver injury [22].
• By contrast, a significant hepatocyte damage was observed in regenerating liver that correlated well with the number of AFP-specific CD8(+) T cells, the activity of liver regeneration, and the level of AFP synthesis [5].
• These data support the hypothesis that during the pre-S phase of liver regeneration, EGF is translocated to the nucleus rather than to lysosomes, and may participate in the initiation of deoxyribonucleic acid synthesis or alteration of gene expression [23].

Associations of Liver Regeneration with chemical compounds

• Tumor necrosis factor (TNF), an inflammatory cytokine, is also important in liver regeneration and hepatocellular growth [24].
• We tested the hypothesis that ethanol impairs liver regeneration by abrogating receptor-mediated elevation of cytosolic free calcium ([Ca2+]i) [25].
• The cellular origin of hepatocyte growth factor (HGF), a polypeptide implicated in liver regeneration, was examined in normal liver and in hepatic regeneration induced by carbon tetrachloride [26].
• Supplemental putrescine, administered at partial hepatectomy and 4 and 8 h thereafter, increased hepatic putrescine concentrations and markedly improved DNA synthesis and liver regeneration in ethanol-fed rats [27].
• It is concluded that chronic ethanol consumption inhibits liver regeneration by a mechanism that is, at least partly, the result of impaired receptor-operated [Ca2+]i signaling due to reduced generation of Ins(1,4,5)P3 [25].

Gene context of Liver Regeneration

• IGF binding protein-1 (IGFBP-1), a hepatocyte-derived secreted protein, is required for normal liver regeneration [28].
• CONCLUSIONS: These results emphasize a central role for IL-6 and soluble IL-6R in liver regeneration and indicate a possible therapeutic potential for the designer cytokine Hyper-IL-6 in clinical situations associated with liver regeneration such as acute hepatic failure or resection of chronically damaged liver tissue [29].
• Amphiregulin: an early trigger of liver regeneration in mice [30].
• Also, during liver regeneration, soluble IL-6R levels were increased [29].
• In contrast, there was a striking reduction in cyclin A (3% vs 16.3%), cyclin B1 (.4% vs 2.3%), and phosphorylated histone 3 protein (0% vs 3.8%) in chronic HCV infection compared with liver regeneration [31].

Analytical, diagnostic and therapeutic context of Liver Regeneration

• None were AFP-positive by radioimmunoassay, despite clinical and biochemical recovery associated with normal liver regeneration [32].
• Neither the rise in IL-6 nor the activation of signal transducer and activator of transcription-3 (STAT3) that is seen during liver regeneration is inhibited by indocin or the selective COX antagonists [33].
• Thymidine kinase activity, mitotic index, a liver mass index and ornithine decarboxylase levels were used as parameters of liver regeneration [34].
• In conclusion, this study suggests that IL-6 could play an important role in limiting hepatic warm ischemia/reperfusion (WI/Rp) injury, probably through its anti-inflammatory properties, modulation of TNF-alpha, and/or promotion of liver regeneration. rIL-6 might become an important cytokine in clinical situations associated with WI/Rp injury [35].
• Uptake of thymidine labeled on carbon 2: a potential index of liver regeneration by positron emission tomography [36].

References