The Role of Heparan Sulfate Proteoglycan, TGF-β1, and Kupffer Cells in Oval Cell Differentiation after Galactosamine (GaIN)-Administration in Mini Rats

Abstract

Six-week-old male Mini rats were intraperitoneally given 1, 000mg/kg of D-galactosamine hydrochloride (GalN) once a week for 4 consecutive weeks and killed at 1, 2, 3, and 5 days (D) and 1, 2, 3, and 4 weeks (W) after the first GalN-administration, respectively. Proliferation of oval cells was observed at and after 3 D. Around them, prominent deposition of heparan sulfate proteoglycans was observed throughout the experimental period. Positive stainability for transforming growth facter (TGF)-β1 was detected in the cytoplasm of both bile duct epithelial cells in the Glisson's capsules and proliferating oval cells throughout the experimental period, and this may suggest an internalization of latent-type TGF-β1 in oval cells as well as bile duct epithelial cells. These results, in turn, indicate the differentiation of oval cells into bile duct epithelial cells. On the other hand, the number of Kupffer cells positive for ED2 peaked at 2D and thereafter decreased gradually, and no spacial relationship was detected between Kupffer cells and proliferating oval cells.