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

Liver Int. 2004 Apr;24(2):161-8. doi: 10.1111/j.1478-3231.2004.0896.x.


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.

MeSH terms

  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / pharmacology
  • Animals
  • Fibroblast Growth Factor 2 / genetics*
  • Fibroblast Growth Factor 2 / metabolism*
  • Hepatectomy
  • Homozygote
  • Indoles / administration & dosage
  • Indoles / pharmacology
  • Injections, Intraperitoneal
  • 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


  • Angiogenesis Inhibitors
  • Indoles
  • Pyrroles
  • RNA, Messenger
  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, mouse
  • Fibroblast Growth Factor 2
  • Semaxinib
  • Vascular Endothelial Growth Factor Receptor-2