Sinusoidal endothelial cell proliferation and expression of angiopoietin/Tie family in regenerating rat liver

J Hepatol. 2001 May;34(5):690-8. doi: 10.1016/s0168-8278(00)00109-4.


Background/aims: Angiogenesis is essential in liver regeneration. However, only little is known about sinusoidal endothelial cell proliferation and the role of different angiogenic growth factors and their receptors during regeneration.

Methods: Seventy percent hepatectomy was carried out on male rats. Serial changes in endothelial cell proliferation were evaluated by immunohistochemistry. The mRNA expressions of angiogenic growth factors (vascular endothelial growth factor (VEGF) and angiopoietins 1 and 2) and their receptors (flt-1, flk-1, Tie-1 and Tie-2) in the whole liver were evaluated by semi-quantitative RT-PCR.

Results: Significant elevation of endothelial cell proliferation started at 48 h and peaked at 72 h after hepatectomy. The ratio of sinusoids to liver tissue area initially decreased at 72 h, and thereafter, significantly increased at 96 h. VEGF related factors had early peaks, which coincided with the endothelial proliferation. flt-1, flk-1 and VEGF expressions peaked at 24, 48 and 72 h, respectively. angiopoietin/Tie factors peaked at 96 h, except Ang-2, which gradually increased and peaked at 168 h.

Conclusions: During liver regeneration, hepatocyte proliferation was followed by endothelial cell proliferation. The VEGF family and angiopoietin/Tie system may have distinct roles in angiogenesis, with an enhanced expression of the VEGF family in the early phase of regeneration followed by angiopoietin/Tie expression.

MeSH terms

  • Angiopoietin-1
  • Angiopoietin-2
  • Animals
  • Cell Aggregation
  • Cell Division / physiology
  • DNA / biosynthesis
  • Endothelial Growth Factors / genetics
  • Endothelium, Vascular / metabolism*
  • Endothelium, Vascular / pathology*
  • Hepatectomy / methods
  • Hepatocytes / metabolism
  • Hepatocytes / pathology
  • Liver Circulation*
  • Liver Regeneration / physiology*
  • Lymphokines / genetics
  • Male
  • Membrane Glycoproteins / metabolism*
  • Neoplasm Proteins / genetics
  • Proteins / metabolism*
  • Proto-Oncogene Proteins*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor, TIE-1
  • Receptor, TIE-2
  • Receptors, Cell Surface / genetics
  • Receptors, Growth Factor / genetics
  • Receptors, TIE
  • Receptors, Vascular Endothelial Growth Factor
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors


  • Angiopoietin-1
  • Angiopoietin-2
  • Angpt1 protein, rat
  • Endothelial Growth Factors
  • Lymphokines
  • MEN1 protein, human
  • Membrane Glycoproteins
  • Neoplasm Proteins
  • Proteins
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Receptors, Cell Surface
  • Receptors, Growth Factor
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • DNA
  • Receptor Protein-Tyrosine Kinases
  • Receptor, TIE-1
  • Receptor, TIE-2
  • Receptors, TIE
  • Receptors, Vascular Endothelial Growth Factor