Pathophysiological Analysis of Prion Protein Expression in the Liver

我们用PCR-selectcDNA消减法发现了活化星状细胞中朊蛋白基因的表达。北方印迹分析表明，PrP mRNA几乎不表达在静止的星状细胞，但其表达显着增强在一个激活的表型。Western blot分析还显示PrP表达以时间依赖性方式增强。原位杂交和免疫组化检测到PrP及其mRNA在肝纤维化模型中的表达，尤其是纤维化隔沿着的细胞外基质物质和平滑肌α-肌动蛋白阳性细胞的表达。此外，PrP的表达被证实在人类患病的肝组织与HBV和HCV诱导的慢性病毒性肝炎和酒精性肝损伤。PrP表达与炎症程度呈正相关。进一步的分析表明PrP的表达与平滑肌α-actin的表达共定位，表明PrP主要在星状细胞中表达。这些结果表明，PrP将作为一种新的肝纤维化的标志物在临床领域。

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.