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首页> 外文期刊>Journal of Cellular Physiology >The complexity of ERK1 and ERK2 MAPKs in multiple hepatocyte fate responses.
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The complexity of ERK1 and ERK2 MAPKs in multiple hepatocyte fate responses.

机译：在多个ERK1的复杂性和ERK2 MAPKs肝细胞命运的反应。

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Recent reports suggest that extracellular signal-regulated kinase (ERK1) and ERK2 mitogen-activated protein kinases (MAPK) may direct specific biological functions under certain contexts. In this study, we investigated the role of early and sustained epidermal growth factor (EGF) stimulation on long-term hepatocyte differentiation and the possible role of ERK1 and ERK2 in this process. We demonstrate a long-term survival and an elevated level of differentiation up to 3 weeks. The differentiation state of hepatocytes is supported by sustained expression of aldolase B, albumin, and the detoxifying enzymes CYP1A2, 2B2, and 3A23. Similarly to freshly isolated cells, cultured hepatocytes also retain the ability to respond to 3-methylcholanthrene (3MC) and phenobarbital (PB), two known CYP inducers. In addition, we show evidence that continuous MAPK/ERK kinase (MEK) inhibition enhances the level of differentiation. Using RNA interference approaches against ERK1 and ERK2, we demonstrate that this effect requires both ERK1 and ERK2 activity, whereas the specific ERK1 knockdown promotes cell survival and the specific ERK2 knockdown regulates cell proliferation. In conclusion, we demonstrate that early and sustained EGF stimulation greatly extends long-term hepatocyte survival and differentiation, and that inhibition of the ERK1/2 MAPK pathway potentiates these pro-survival/pro-differentiation phenotypes. We clearly attest that specific ERK1 and ERK2 MAPKs determine hepatocyte survival and proliferation, respectively, whereas dual inhibition is required to stabilize a highly differentiated state.
机译：最近的报告表明,细胞外signal-regulated激酶(ERK1)和ERK2增殖蛋白激酶(MAPK)直接下特定的生物功能特定的上下文。早期和持续的表皮生长的作用对长期肝细胞刺激因子(EGF)分化和ERK1的可能作用在这一过程中ERK2。生存和分化的高水平3周。肝细胞是由持续表达醛缩酶B、白蛋白和排毒酶CYP1A2, 2 b2, 3 a23。刚分离细胞,培养肝细胞保持反应能力3-methylcholanthrene (3 mc)和苯巴比妥(PB),两个已知的CYP抗病诱导剂。显示的证据表明,连续MAPK / ERK激酶(MEK)抑制水平的提高分化。方法对ERK1和ERK2,我们证明这需要ERK1和ERK2的影响活动,而特定的ERK1击倒促进细胞生存和特定的ERK2可拆卸的调节细胞增殖。结论,我们证明早期持续EGF刺激大大扩展了长期肝细胞生存和的分化,抑制ERK1/2 MAPK途径强化pro-survival / pro-differentiation表型。清楚地证明,具体ERK1和ERK2 MAPKs确定肝细胞生存和扩散,分别,而双重抑制作用是必需的稳定高度分化状态。

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