Immunolocalization of hepatocyte growth factor and its receptor (c-Met) during mouse liver development

Kiyoshi S. Ishikawa, Tohru Masui, Katsutoshi Ishikawa, Nobuyoshi Shiojiri

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)


Although hepatocyte growth factor (HGF) was discovered as a potent hepatotrophic factor responsible for liver regeneration and may involve some organ development in embryogenesis, it remains to be revealed what roles HGF plays in liver development. The present study was undertaken to determine which cells express HGF and its receptor c-Met and when c-Met is activated in mouse liver development by using immunoblotting and immunohistochemical techniques. HGF was detected in hepatocytes and non-parenchymal cells, including biliary epithelial cells, periportal connective tissue cells, megakaryocytes, endothelial cells, and sinusoidal cells, throughout liver development. Positive HGF immunostaining in hepatocytes increased during postnatal development, and reached the maximal level in the adult stage. c-Met protein was also expressed in hepatocytes throughout liver development, but maximal staining was obtained in 1- or 2-week-old livers. Phosphorylation of tyrosine residues in the c-Met β chain also occurred in these stages. These results suggest that HGF signaling is implicated in hepatocyte growth during postnatal liver development, and its action could be in a paracrine mode; HGF produced by non-parenchymal cells such as sinusoidal cells acts on hepatocytes expressing c-Met receptors. Positive immunostaining in adult and postnatal hepatocytes may be derived from their blood clearance of HGF.

Original languageEnglish
Pages (from-to)453-462
Number of pages10
JournalHistochemistry and Cell Biology
Issue number5
Publication statusPublished - 2001
Externally publishedYes


  • Growth
  • HGF
  • Hepatocytes
  • Mouse
  • c-Met

ASJC Scopus subject areas

  • Histology
  • Molecular Biology
  • Medical Laboratory Technology
  • Cell Biology


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