Expression of CD44 in rat hepatic progenitor cells.

BACKGROUND/AIMS: 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.