Schulze F, Schardt K, Wedemeyer I, Konze E, Wendland K, Dirsch O, Töx U, Dienes H P, Odenthal M
Institut für Pathologie, Universitätsklinikum Köln.
Verh Dtsch Ges Pathol. 2007;91:250-6.
The conversion of epithelial cells in a mesenchymal cell type is called "epithelial-mesenchymal-transition" (EMT). This process is defined by a loss of epithelial specific characteristics such as cell adhesion, polarity and a reorganization of cytoskeletal proteins. EMT has been shown to be involved in progression of cancer and in obstructive renal fibrosis. In this study we analyzed liver tissues in a bile-duct ligation model of rats and human liver biopsies with cholestatic fibrosis and chronic hepatitis c infection to determine if biliary epithelial cells undergo phenotypical and functional changes during chronic injury.
Liver tissue of rats and human patients was examined by immunohistochemistry using antibodies against epithelial and mesenchymal specific targets as well as molecules of potentially activated signaling pathways. To study contribution of biliary epithelial cells in extracellular matrix production we performed laser microdissection combined with real-time PCR.
Bile duct ligation in rats induced a prominent biliary epithelial proliferation and a pronounced expression of vimentin was observed in biliary epithelial cells, whereas no vimentin expression was detectable in bile duct cells of sham operated rats. In human liver biopsies from patients with cholestatic fibrosis and chronic hepatitis c infection a prominent biliary expression of vimentin could be shown. Despite this, epithelial marker proteins were still detectable. Further, we observed collagen I mRNA expression in laser microdissected bile ducts.
Biliary epithelial cells show cytoskeletal rearrangements during chronic liver injury towards a mesenchymal phenotype. The detection of collagen I mRNA in bile duct cells suggests that they might participate in extracellular matrix production.
上皮细胞向间充质细胞类型的转变称为“上皮-间充质转化”（EMT）。这一过程的定义是上皮特异性特征的丧失，如细胞黏附、极性以及细胞骨架蛋白的重新组织。EMT已被证明与癌症进展和梗阻性肾纤维化有关。在本研究中，我们分析了大鼠胆管结扎模型中的肝组织以及患有胆汁淤积性纤维化和慢性丙型肝炎感染的人类肝活检组织，以确定胆管上皮细胞在慢性损伤过程中是否经历表型和功能变化。
使用针对上皮和间充质特异性靶点以及潜在激活信号通路分子的抗体，通过免疫组织化学检查大鼠和人类患者的肝组织。为了研究胆管上皮细胞在细胞外基质产生中的作用，我们进行了激光显微切割结合实时PCR。
大鼠胆管结扎诱导了显著的胆管上皮增殖，并且在胆管上皮细胞中观察到波形蛋白的明显表达，而在假手术大鼠的胆管细胞中未检测到波形蛋白表达。在患有胆汁淤积性纤维化和慢性丙型肝炎感染的人类肝活检组织中，可以显示波形蛋白在胆管中的显著表达。尽管如此，上皮标记蛋白仍然可以检测到。此外，我们在激光显微切割的胆管中观察到I型胶原mRNA表达。
胆管上皮细胞在慢性肝损伤过程中表现出细胞骨架重排，趋向间充质表型。胆管细胞中I型胶原mRNA的检测表明它们可能参与细胞外基质的产生。
