Expression of CD44 in rat hepatic progenitor cells.
OBJECTIVE
Small hepatocytes (SHs) are hepatic progenitor cells, but the phenotypical difference between SHs and mature hepatocytes (MHs) has never been demonstrated.


METHODS
The profile of gene expression was examined to clarify the difference between SHs and MHs by using a DNA microarray. Genes that were specifically expressed in SHs were identified and RT-PCR analysis of them was performed. Immunocytochemistry for CD44 standard form (CD44s) and variant form 6 (CD44v6) was performed using cultured SHs and the d-galactosamine (GalN)-injured rat liver. From the GalN-treated liver, CD44s+ cells were obtained by sorting and RT-PCR analysis was performed.


RESULTS
Analysis using the DNA microarray and RT-PCR of them revealed restricted expression of CD44s and CD44v6 in SHs. In culture, CD44s appeared at day 3 and increased with the proliferation of SHs. CD44v6 expression was delayed compared to that of CD44s. With GalN-administration, CD44+ hepatocytes appeared around periportal areas at days 3 and 4 and then decreased. Sorted CD44s+ cells could form colonies and possessed hepatic markers.


CONCLUSIONS
CD44 is a specific marker of SHs. The expression of CD44 mRNA and protein is restricted to SHs, and is up-regulated at the time when SHs start to proliferate both in vitro and in vivo.
Department of Pathophysiology, Cancer Research Institute, Sapporo Medical University School of Medicine, South-1, West-17, Chuo-Ku, Sapporo 060-8556, Japan.
Junko
J
Kon
Hidekazu
H
Ooe
Hideki
H
Oshima
Yamato
Y
Kikkawa
Toshihiro
T
Mitaka
D000818:Animals; D018929:Cell Culture Techniques; D017931:DNA Primers; D005786:Gene Expression Regulation; D022781:Hepatocytes / Q000166:cytology / Q000502:physiology*; D018960:Hyaluronan Receptors / Q000235:genetics*; D007150:Immunohistochemistry; D008099:Liver / Q000166:cytology* / Q000502:physiology*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*
D017931:DNA Primers; D018960:Hyaluronan Receptors