EPITHELIAL-MESENCHYMAL TRANSITION IN CULTURED NEONATAL HEPATOCYTES
EPITHELIAL-MESENCHYMAL TRANSITION IN CULTURED NEONATAL HEPATOCYTES
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DOI：
10.1002/hep.1840210332
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发表时间：
1995-03-01
期刊：
影响因子：
13.5
通讯作者：
VILARO, S
中科院分区：
文献类型：
--
作者：
PAGAN, R;LLOBERA, M;VILARO, S
当肝细胞富集的馏分从新生大鼠肝脏培养不同的时间在没有添加生长因子，人口的高度增殖和迁移成纤维细胞样细胞出现。细胞角蛋白和波形蛋白抗体的双重免疫荧光显示，细胞角蛋白阳性细胞的数量逐渐减少，与波形蛋白阳性细胞的增加平行。一些移行上皮或迁移形态的细胞共表达两种中间丝蛋白。免疫荧光与肝细胞分化标志物的抗体显示，接种后不久，大多数细胞的抗白蛋白抗体呈阳性，但在培养1周后，只有10%呈阳性。呈现白蛋白和细胞角蛋白的细胞出现形态上皮。成纤维细胞样细胞对白蛋白不呈阳性，但一些具有移行上皮形态的细胞呈现白蛋白和波形蛋白的一些标记。谷胱甘肽-S-转移酶亚基Pi和波形蛋白的抗体的免疫荧光显示，许多成纤维细胞样细胞对两种标记物呈阳性，其中一些是双核细胞。在地塞米松存在下，在精氨酸不存在下进行培养，或I型胶原基质对新生肝细胞的行为没有影响。成纤维细胞样细胞的出现是个体发育调节的，因为在7天和15日龄动物肝脏的细胞培养物中观察到波形蛋白阳性细胞百分比的最高增加。这些数据提供的证据表明，培养的新生肝细胞有可能通过上皮-间充质转化去分化，并有助于了解肝脏的生长发育。
When hepatocyte-enriched fractions from neonatal rat livers were cultured for different times in the absence of added growth factors, a population of highly proliferating and migrating fibroblastlike cells appeared. Double immunofluorescence with antibodies to cytokeratin and to vimentin showed a progressive reduction in the number of cytokeratin-positive cells parallel to an increase in the vimentin-positive cells. Some cells with transitional epithelial or migrating morphology coexpressed both intermediate filament proteins. Immunofluorescence with antibodies against hepatocyte differentiation markers showed that shortly after seeding most of the cells were positive to anti-albumin antibodies, but after 1 week in culture, only 10% were positive. Cells presenting albumin and cytokeratin appeared morphologically epithelial. Fibroblastlike cells were not positive for albumin, but some cells with transitional epithelial morphology presented some labels for albumin and for vimentin, Immunofluorescence with antibodies to glutathione-S-transferase subunit Pi and vimentin showed that many fibroblastlike cells were positive for both markers, some of them binucleate, Cultures performed in the presence of dexamethasone, absence of arginine, or on collagen type I matrix had no effect on the behavior of neonatal hepatocytes. The appearance of fibroblastlike cells was ontogenically regulated because the highest increase in the percentage of vimentin-positive cells was observed in cell cultures from livers of 7- and 15-day-old animals. These data provide evidence that neonatal hepatocytes in culture have the potential to dedifferentiate by epithelial-mesenchymal transition and contribute to an understanding of hepatic growth development.