Pathophysiological Analysis of Prion Protein Expression in the Liver

我们用聚合酶链式反应-选择基因消减的方法发现了活化的星状细胞中PrP基因的表达。Northern杂交分析表明，PrP mRNA在静止的星状细胞中几乎不表达，但在激活的表型中其表达显著增强。Western印迹分析还显示PrP的表达呈时间依赖性增强。原位杂交和免疫组织化学方法检测到PrP及其m RNA在肝纤维化模型中的表达，尤其是沿纤维间隔堆积细胞外基质和平滑肌α-肌动蛋白阳性细胞。此外，在乙肝病毒和丙型肝炎所致慢性病毒性肝炎和酒精性肝损伤的人的病变肝组织中也证实了PrP的表达。PRP表达与炎症严重程度呈正相关。进一步的分析表明，PrP的表达与平滑肌α-肌动蛋白的表达共同定位，表明PrP主要在星状细胞中表达。这些结果表明PrP可作为一种新的肝纤维化标志物应用于临床。

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.