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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Main Authors: Sturm, Jörg (Author) , Keese, Michael (Author) , Zhang, Honyue (Author) , Bönninghoff, Roderich (Author) , Magdeburg, Richard (Author) , Vajkoczy, Peter (Author) , Dono, Rosanna (Author) , Zeller, Rolf (Author) , Gretz, Norbert (Author)
Format: Article (Journal)
Language:English
Published: 01 April 2004
In: Liver international
Year: 2004, Volume: 24, Issue: 2, Pages: 161-168
ISSN:1478-3231
DOI:10.1111/j.1478-3231.2004.0896.x
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1111/j.1478-3231.2004.0896.x
Verlag, lizenzpflichtig, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1478-3231.2004.0896.x
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Author Notes:Jörg Sturm, Michael Keese, Honyue Zhang, Roderich Bönninghoff, Richard Magdeburg, Peter Vajkoczy, Rosanna Dono, Rolf Zeller, Norbert Gretz
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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.
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Physical Description:Online Resource
ISSN:1478-3231
DOI:10.1111/j.1478-3231.2004.0896.x