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首页> 外文期刊>Journal of Cellular Physiology >The transforming growth factor-beta (TGF-beta) mediates acquisition of a mesenchymal stem cell-like phenotype in human liver cells.
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The transforming growth factor-beta (TGF-beta) mediates acquisition of a mesenchymal stem cell-like phenotype in human liver cells.

机译：转化生长因子(及)间充质干细胞介导的收购在人类肝细胞细胞样的表型。

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Transforming growth factor-beta (TGF-beta) mediates several and sometime opposite effects in epithelial cells, inducing growth inhibition, and apoptosis but also promoting an epithelial to mesenchymal transition (EMT) process, which enhances cell migration and invasion. TGF-beta plays relevant roles in different liver pathologies; however, very few is known about its specific signaling and cellular effects in human primary hepatocytes. Here we show that TGF-beta inhibits proliferation and induces pro-apoptotic genes (such as BMF or BIM) in primary cultures of human fetal hepatocytes (HFH), but also up-regulates anti-apoptotic genes, such as BCL-XL and XIAP. Inhibition of the epidermal growth factor receptor (EGFR), using gefitinib, abrogates the increase in the expression of the anti-apoptotic genes and significantly enhances cell death. Simultaneously, TGF-beta is able to induce an EMT process in HFH, coincident with Snail up-regulation and a decrease in E-cadherin levels, cells showing mesenchymal proteins and reorganization of the actin cytoskeleton in stress fibers. Interestingly, these cells show loss of expression of specific hepatic genes and increased expression of stem cell markers. Chronic treatment with TGF-beta allows selection of a population of mesenchymal cells with a de-differentiated phenotype, reminiscent of progenitor-like cells. Process is reversible and the mesenchymal stem-like cells re-differentiate to hepatocytes under controlled experimental conditions. In summary, we show for the first time that human hepatocytes may respond to TGF-beta inducing different signals, some of them might contribute to tumor suppression (growth inhibition and apoptosis), but others should mediate liver tumor progression and invasion (EMT and acquisition of a stem-like phenotype).
机译：转化生长因子(及)协调几个有时候相反的效应上皮细胞,诱导生长抑制促进一个上皮细胞凋亡也间充质转变(EMT)过程,增强细胞迁移和入侵。扮演相关角色在不同的肝脏病态的;特定的信号和在人类细胞的影响主要的肝细胞。抑制增殖和诱导pro-apoptotic基因(如BMF或女子)的主要文化人类胎儿肝细胞(仁人家园)分部,但也让抗凋亡基因,如BCL-XLXIAP。因子受体(EGFR),使用吉非替尼,废除的增加表达的抗凋亡基因和显著增强细胞死亡。诱导一个EMT过程,仁人家园能够重合蜗牛上调和钙粘蛋白减少水平,显示间充质蛋白质和细胞肌动蛋白细胞骨架的重组应力纤维。特定的肝基因表达的和损失增加干细胞标记物的表达。慢性治疗及允许选择人口的间充质细胞去分化表型,让人想起progenitor-like细胞。间充质干细胞细胞re-differentiate肝细胞在实验控制条件。人类肝细胞响应的时间及诱导不同的信号,其中的一些可能导致肿瘤抑制增长抑制细胞凋亡),但其他人应该调节肝脏肿瘤进展和入侵(EMT)和收购的干细胞表型)。

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