Expression of placental growth factor in regenerating livers after partial hepatectomy in the rat

Eur J Gastroenterol Hepatol. 2011 Jan;23(1):66-75. doi: 10.1097/MEG.0b013e328341ef35.

Abstract

Background/aims: Placental growth factor (PlGF) is known for its role in pathological conditions to protect parenchymal cells of different organs from injury, whereas its presence in the liver and its potential importance in stimulating liver regeneration has never been described. This was investigated in this study using a rat model of partial hepatectomy (PH).

Methods: The rat model of 70, 80, and 90% PH was used. Liver samples were taken peroperatively, 1 h, 1, 2, 3, and 7 days after surgery. Liver regeneration was evaluated by liver weight/body weight ratio, liver regeneration rate (%), and proliferating cell marker Ki67. The expression of PlGF, vascular endothelial growth factor (VEGF), VEGF receptor 1 (Flt-1), VEGF receptor 2 (Flk-1), and hypoxia inducible factor-1α mRNA was measured by quantitative real-time PCR and localized by immunohistochemistry.

Results: The mRNA expression of PlGF was upregulated immediately after PH. Compared with 70 and 80% PH groups, the 90% PH group had a significantly lower PlGF and hypoxia inducible factor-1α mRNA expression, in parallel to a delayed liver weight/body weight ratio recovery. Only little differences were observed in VEGF, Flt-1, and Flk-1 mRNA expression among the PH groups.

Conclusion: This study shows for the first time the PlGF upregulation in regenerating livers, which is related to hypoxia stimulation and liver growth. The swift PlGF upregulation immediately after PH may indicate an important role for the PlGF/Flt-1 pathway in the early stage of liver regeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Hepatectomy
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Ki-67 Antigen / metabolism
  • Liver Regeneration*
  • Male
  • Placenta Growth Factor
  • Pregnancy Proteins / metabolism*
  • Rats
  • Rats, Inbred Lew
  • Up-Regulation
  • Vascular Endothelial Growth Factor Receptor-1 / metabolism
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism
  • Vascular Endothelial Growth Factors / metabolism

Substances

  • Hif1a protein, rat
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Ki-67 Antigen
  • Pgf protein, rat
  • Pregnancy Proteins
  • Vascular Endothelial Growth Factors
  • Placenta Growth Factor
  • Flt1 protein, rat
  • Vascular Endothelial Growth Factor Receptor-1
  • Vascular Endothelial Growth Factor Receptor-2