Epimorphin is involved in differentiation of rat hepatic stem-like cells through cell-cell contact.
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 gamma-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.
First Department of Internal Medicine, Akita University School of Medicine, Akita, Japan.
Kouichi
K
Miura
Hirokazu
H
Nagai
Yasuharu
Y
Ueno
Takashi
T
Goto
Ken-ichiro
K
Mikami
Kunio
K
Nakane
Kazuo
K
Yoneyama
Daisuke
D
Watanabe
Kunihiko
K
Terada
Toshihiro
T
Sugiyama
Katsuyuki
K
Imai
Haruki
H
Senoo
Sumio
S
Watanabe
D000818:Animals; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D018920:Coculture Techniques / Q000379:methods; D022781:Hepatocytes / Q000166:cytology* / Q000187:drug effects; D008297:Male; D008562:Membrane Glycoproteins / Q000494:pharmacology / Q000502:physiology*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D008562:Membrane Glycoproteins; C504581:Stx2 protein, rat