Liver regeneration in FGF-2-deficient mice: VEGF acts as potential functional substitute for FGF-2

Background/Aims: The angiogenic properties, its role in mesoderm differentiation and cell culture studies implicate an important role of fibroblast growth factor (FGF‐2) in liver regeneration. The aim of the study was to evaluate this role in a FGF‐2 knockout mouse model. Methods: Liver regeneration...

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Bibliographic Details
Published in:Liver international 2004-04, Vol.24 (2), p.161-168
Main Authors: Sturm, Jörg, Keese, Michael, Zhang, Honyue, Bönninghoff, Roderich, Magdeburg, Richard, Vajkoczy, Peter, Dono, Rosanna, Zeller, Rolf, Gretz, Norbert
Format: Article
Language:English
Subjects:
angiogenesis
Angiogenesis Inhibitors - administration & dosage
Angiogenesis Inhibitors - pharmacology
Animals
bFGF
Cellular Biology
FGF-2
FGF-2 deficient mice
Fibroblast Growth Factor 2 - genetics
Fibroblast Growth Factor 2 - metabolism
Hepatectomy
HGF
Homozygote
Indoles - administration & dosage
Indoles - pharmacology
Injections, Intraperitoneal
Life Sciences
liver regeneration
Liver Regeneration - drug effects
Liver Regeneration - physiology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Neovascularization, Pathologic - metabolism
Pyrroles - administration & dosage
Pyrroles - pharmacology
RNA, Messenger - genetics
RNA, Messenger - metabolism
Vascular Endothelial Growth Factor A - genetics
Vascular Endothelial Growth Factor A - metabolism
Vascular Endothelial Growth Factor Receptor-2 - antagonists & inhibitors
VEGF
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Summary:Background/Aims: The angiogenic properties, its role in mesoderm differentiation and cell culture studies implicate an important role of fibroblast growth factor (FGF‐2) in liver regeneration. The aim of the study was to evaluate this role in a FGF‐2 knockout mouse model. Methods: Liver regeneration after left hemihepatectomy (partial hepatectomy, PH) was evaluated in homozygous FGF‐2 deficient (−/−) mice (male C57BL/6J) and their FGF‐2 competent (+/+) littermates (controls) (day 0–10). Results: FGF‐2‐(−/−) mice displayed normal dynamics in liver regeneration. FGF‐2 protein was overexpressed 4 days post PH in controls. BrdU incorporation showed a biphasic pattern in FGF‐2‐(−/−) mice, whereas it decreased continuously after one peak (day 2) in controls. In FGF‐2‐(−/−) livers hepatic growth factor mRNA post PH was 1 day longer decreased and markedly less elevated thereafter compared with control. Vascular endothelial growth factor (VEGF) mRNA levels were clearly increased in FGF‐2‐(−/−) mice pre‐ and postoperatively in contrast to controls. VEGF protein levels in livers of FGF‐2‐(−/−) mice were elevated preoperatively, but similar in both groups after PH. With SU5416, a VEGF‐receptor inhibitor, liver regeneration in FGF‐2‐(−/−) mice was reduced significantly, whereas it remained unchanged in controls. Conclusions: Liver regeneration dynamics in FGF‐2‐(−/−) mice were comparable with controls, potentially due to a functional substitution of FGF‐2 by VEGF.
ISSN:1478-3223
1478-3231
DOI:10.1111/j.1478-3231.2004.0896.x