Expression of prion protein in activated hepatic stellate cells

To clone genes associated with the activation of hepatic stellate cells, suppression subtractive hybridization was employed and thirteen genes were found to be dominantly expressed in activated stellate cells. Among them, one was 100% identical to the 421-837th base pairs of cDNA sequence reported for rat prion-related protein (PrP). Northern blot analysis demonstrated that PrP mRNA expression increased in cultured stellate cells in a time-dependent manner, while it was hardly detected in freshly isolated ones. As demonstrated by in situ hybridization, PrP mRNA was localized in and around the fibrous septa of carbon tetrachloride (CCl4)-treated liver. Western blot analysis confirmed the expression of PrP in cultured stellate cells and further demonstrated that expression of PrP as well as that of smooth muscle alpha-actin increased in cultured stellate cells in a rime-dependent manner. Moreover, PrP was detected immunohistochemically in the fibrous septa of CCl4-damaged liver and sinusoidal linings of common bile duct-ligated liver. These results indicate that PrP gene and protein are dominantly expressed in activated stellate cells.