Pathophysiological Analysis of Prion Protein Expression in the Liver

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We have discovered the prion protein (PrP) gene expression in activated stellate cells by using PCR-select cDNA subtraction method. Northern blot analysis revealed that PrP mRNA was hardly expressed in quiescent stellate cells, but its expression was dramatically augmented in an activated phenotype. Western blot analysis also revealed that PrP expression was enhanced in a time-dependent manner. In in situ hybridization and in imunohistochemistry, PrP and its mRNA expression was detected in liver fibrosis model, in particular along the fibrotic septum accumulating extracellular matrix materials and smooth muscle α-actin-positive cells. In addition, PrP expression was confirmed in human diseased liver tissue with HBV and HCV-induced chronic viral hepatitis and alcoholic liver damage. PrP expression had positive relationship with inflammatory severity. Further analysis indicated that PrP expression was co-localized with the expression of smooth muscle α-actin, indicating that PrP was expressed dominantly in stellate cells. These results indicate that PrP would be utilized as a novel marker for liver fibrosis in the clinical field.