Altered apoptotic response and different liver structure during liver regeneration in FGF-2-deficient mice

Cell Physiol Biochem. 2004;14(4-6):249-60. doi: 10.1159/000080334.

Abstract

Background/aims: To investigate postulated differences related to FGF-2 in liver morphology and expression of apoptosis-related factors after partial hepatectomy (PH).

Methods: Homogenous FGF-2-deficient mice (C57BL/6J) with their FGF-2-(+/+) littermates (control) were used to examine the structure of regenerating livers after PH with light and electron microscopy. The regenerative response and BrDu incorporation were monitored. The expression of BclX-l, Bax, Fas, TNF-alpha, and Caspase-3 were measured by reverse transcription PCR (RT-PCR) and Northern blot analysis.

Results: In the FGF-2-(-/-) group, hepatocytes and endothelial cells contain mitochondria with atypical cristae and fragmented endoplasmic reticulum structures compared to control. Sinusoids show irregular basal laminae. These changes are in accordance with a differential expression of apoptosis-related factors: FasL was expressed throughout the entire observation span (days 0 to 10 post-PH). Following PH, tumor necrosis factor alpha (TNFalpha)-mRNA levels were higher in FGF-2-(+/+) animals, while Fas as well as Bax and BclXl were overexpressed in FGF-2-(-/-) mice. Caspase-3-mRNA was similarly expressed in both groups, but Caspase-3 activity was elevated for 4 days in FGF-2-(-/-) mice.

Conclusion: Despite morphologic differences, differences in the time schedule of DNA synthesis and differences in apoptotic response, the dynamics of liver regeneration in FGF-2-(-/-) mice were not impaired.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Apoptosis / physiology*
  • Caspase 3
  • Caspases / analysis
  • Caspases / genetics
  • Caspases / metabolism
  • Cell Size
  • Endoplasmic Reticulum / ultrastructure
  • Fas Ligand Protein
  • Fibroblast Growth Factor 2 / genetics*
  • Fibroblast Growth Factor 2 / physiology
  • Gene Expression
  • Hepatectomy
  • Hepatocytes / chemistry
  • Hepatocytes / physiology
  • Hepatocytes / ultrastructure*
  • Liver / ultrastructure
  • Liver Regeneration / genetics
  • Liver Regeneration / physiology*
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Mutant Strains
  • Mitochondria / ultrastructure
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • RNA, Messenger / analysis
  • RNA, Messenger / metabolism
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism
  • bcl-2-Associated X Protein
  • bcl-X Protein
  • fas Receptor / genetics
  • fas Receptor / metabolism

Substances

  • Bax protein, mouse
  • Bcl2l1 protein, mouse
  • Fas Ligand Protein
  • Fasl protein, mouse
  • Membrane Glycoproteins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • bcl-2-Associated X Protein
  • bcl-X Protein
  • fas Receptor
  • Fibroblast Growth Factor 2
  • Casp3 protein, mouse
  • Caspase 3
  • Caspases