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

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

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.

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.

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.