Epimorphin is involved in differentiation of rat hepatic stem-like cells through cell-cell contact

Kouichi Miura, Hirokazu Nagai, Yasuharu Ueno, Takashi Goto, Ken Ichiro Mikami, Kunio Nakane, Kazuo Yoneyama, Daisuke Watanabe, Kunihiko Terada, Toshihiro Sugiyama, Katsuyuki Imai, Haruki Senoo, Sumio Watanabe

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)

Abstract

Epimorphin, a mesenchymal cell surface-associated molecule, is detected on hepatic stellate cells (HSCs) in the liver. Here, we show the involvement of epimorphin in differentiation of rat hepatic stem-like cells (HSLCs) through contact with HSCs. HSLCs, isolated from adult rats, cultured in stellate cell-conditioned medium had no phenotypic and morphological changes, whereas HSLCs co-cultured with HSCs expressed albumin, transferrin, and tyrosine aminotransferase. An anti-epimorphin antibody inhibited hepatocytic differentiation of HSLCs in co-culture. Furthermore, epimorphin induced mRNA expression of albumin, transferrin, tyrosine aminotransferase, and γ-glutamyl transpeptidase with decrease of c-kit and musashi-1. Morphologically, HSLCs piled up when co-cultured with HSCs, which was dramatically inhibited by an anti-epimorphin antibody. HSLCs contact with epimorphin started piling up, changed their shape from flat to cuboidal, and subsequently developed bile-canaliculi-like structures. In conclusion, epimorphin is a factor that induces differentiation of hepatic stem-like cells through epithelial-mesenchymal cell contact.

Original languageEnglish
Pages (from-to)415-423
Number of pages9
JournalBiochemical and biophysical research communications
Volume311
Issue number2
DOIs
Publication statusPublished - 2003 Nov 14
Externally publishedYes

Keywords

  • Cell surface-associated molecule
  • Differentiation
  • Epimorphin
  • Epithelial-mesenchymal interaction
  • Stem cell

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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