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


CONCLUSIONS
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.
Chirurgische Klinik, Universitätsklinikum Mannheim, Germany. joerg.strum@chir.ma.uni-heidelberg.de
Jörg W
JW
Sturm
Hongyu
H
Zhang
Richard
R
Magdeburg
Till
T
Hasenberg
Roderich
R
Bönninghoff
Jasmina
J
Oulmi
Michael
M
Keese
Robert
R
McCuskey
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D053148:Caspase 3; D020169:Caspases / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D048429:Cell Size; D004721:Endoplasmic Reticulum / Q000648:ultrastructure; D053222:Fas Ligand Protein; D016222:Fibroblast Growth Factor 2 / Q000235:genetics* / Q000502:physiology; D015870:Gene Expression; D006498:Hepatectomy; D022781:Hepatocytes / Q000737:chemistry / Q000502:physiology / Q000648:ultrastructure*; D008099:Liver / Q000648:ultrastructure; D008115:Liver Regeneration / Q000235:genetics / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D008928:Mitochondria / Q000648:ultrastructure; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism
C494827:Bax protein, mouse; C494812:Bcl2l1 protein, mouse; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D019014:fas Receptor; D016222:Fibroblast Growth Factor 2; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases