Dezso Katalin, Jelnes Peter, László Viktória, Baghy Kornélia, Bödör Csaba, Paku Sándor, Tygstrup Niels, Bisgaard Hanne Cathrine, Nagy Peter
First Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary.
Am J Pathol. 2007 Nov;171(5):1529-37. doi: 10.2353/ajpath.2007.070273. Epub 2007 Sep 20.
Thy-1, a marker of hematopoietic stem cells, has been reported to be expressed by oval cells proliferating during stem cell-mediated regeneration in rat liver, suggesting a relationship between the two cell populations. Consequently, Thy-1 has become an accepted cell surface marker to sort hepatic oval cells. In the present study we used the well-characterized 2-acetylaminfluorene/partial hepatectomy model to induce transit-amplification of hepatic oval cells in the regenerating liver and characterized Thy-1 expression using Northern hybridization, quantitative reverse transcriptase-polymerase chain reaction analysis, immunofluorescence confocal microscopy, and immunoelectronmicroscopy. We found that Thy-1 expression was induced during transit-amplification of the oval cell population, but Thy-1 mRNA was not present in the alpha-fetoprotein-expressing oval cells. Thy-1 protein was consistently present outside the basement membrane surrounding the oval cells. It overlapped frequently with smooth muscle actin staining. A similar cellular localization of the Thy-1 protein was found on human liver specimens with ductular reactions obtained from patients with fulminant liver failure. Furthermore, Thy-1 was expressed by myofibroblasts in experimental liver fibrosis models without oval cell proliferation. We conclude that Thy-1 is not a marker of oval cells but is present on a subpopulation of myofibroblasts/stellate cells.
Thy-1是造血干细胞的一种标志物,据报道,在大鼠肝脏干细胞介导的再生过程中增殖的卵圆细胞可表达Thy-1,这表明这两种细胞群体之间存在关联。因此,Thy-1已成为一种公认的用于分选肝卵圆细胞的细胞表面标志物。在本研究中,我们使用了特征明确的2-乙酰氨基芴/部分肝切除术模型来诱导再生肝脏中肝卵圆细胞的过渡扩增,并使用Northern杂交、定量逆转录聚合酶链反应分析、免疫荧光共聚焦显微镜和免疫电子显微镜对Thy-1的表达进行了表征。我们发现,在卵圆细胞群体的过渡扩增过程中Thy-1表达被诱导,但在表达甲胎蛋白的卵圆细胞中不存在Thy-1 mRNA。Thy-1蛋白始终存在于围绕卵圆细胞的基底膜之外。它经常与平滑肌肌动蛋白染色重叠。在暴发性肝衰竭患者获得的有小胆管反应的人肝脏标本上发现了Thy-1蛋白类似的细胞定位。此外,在没有卵圆细胞增殖的实验性肝纤维化模型中,肌成纤维细胞表达Thy-1。我们得出结论,Thy-1不是卵圆细胞的标志物,而是存在于肌成纤维细胞/星状细胞亚群上。