Expression of cellular prion protein in activated hepatic stellate cells.

Suppression subtractive hybridization was used to clone genes associated with the activation of hepatic stellate cells and 13 genes were found to be dominantly expressed in activated stellate cells. Among them, one was identical to the 421-837th base pairs of cDNA sequence reported for rat prion-related protein (PrP). In cultured stellate cells, PrP mRNA expression increased in a time-dependent manner in parallel with smooth muscle (SM) alpha-actin mRNA expression. In situ hybridization demonstrated that PrP mRNA was localized in and around the fibrous septa of carbon tetrachloride (CCl4)-treated liver. Cellular PrP (PrPc) was produced by culture-activated stellate cells, and immunohistochemically detected in the fibrous septa of CCl4-damaged liver and sinusoidal linings of common bile duct-ligated liver, consistent with the localization of SM alpha-actin. Immunoelectron microscopy revealed that PrPc resided on the plasma membrane of stellate cells. These results indicate that PrP expression is closely related to stellate cell activation associated with fibrogenic stimuli.