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Involvement of metastasis tumor antigen 1 in hepatic regeneration and proliferation

机译:转移性肿瘤抗原1参与肝再生和增殖

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Background/Aims: Metastasis tumor antigen 1 (MTA1), an integral part of nucleosome remodeling and histone deacetylation (NuRD) complexes, is well correlated with the potential of metastasis, with the ability to regulate divergent cellular pathways by modifying the acetylation status of crucial target genes. However, additional biological functions of this molecule remain largely unexplored. This study was undertaken to explore the potential role of this molecule in mouse liver. Methods: MTA1 expression was firstly explored in mouse partial hepatectomy model (PHx). The effect of overexpression of MTA1 on hepatic proliferation and differentiation was then examined in vivo by hydrodynamic-based gene transfer method and in vitro using transformed cell line AML12 overexpressing MTA1, respectively. Results: Consistent with the hepatic regeneration, MTA1 expression was significantly increased 24h post-PHx, with a maximum level at 48h after PHx. MTA1 immunoreactivity was generally elevated right after PHx and the staining appeared to experience a cytoplasm-to-nuclear transition. Overexpression of exogenous MTA1 could notably stimulate hepatic proliferation in vivo and could also accelerate hepatocyte differentiation in vitro. Conclusion: These data underscore a hepatocelluar facet of this recently defined molecule, which may represent as a novel regulator and a new therapeutic target for the treatment of impaired liver.
机译:背景/目的:转移性肿瘤抗原1(MTA1)是核小体重塑和组蛋白去乙酰化(NuRD)复合物的组成部分,与转移的潜力密切相关,并具有通过改变关键的乙酰化状态来调节不同细胞途径的能力。靶基因。但是,该分子的其他生物学功能在很大程度上仍未开发。进行这项研究以探索该分子在小鼠肝脏中的潜在作用。方法:首先在小鼠部分肝切除模型(PHx)中探讨MTA1的表达。然后分别通过基于流体动力学的基因转移方法在体内和体外分别使用过表达MTA1的转化细胞系AML12来检查MTA1过表达对肝细胞增殖和分化的影响。结果:与肝再生一致,PHX后24h M​​TA1表达显着增加,PHx后48h达到最高水平。 PHx后,MTA1的免疫反应性通常会升高,并且染色似乎经历了细胞质到核的过渡。外源MTA1的过表达可以显着刺激体内肝脏的增殖,还可以促进体外肝细胞的分化。结论:这些数据强调了这个最近定义的分子的肝细胞表面,它可能代表着一种新的调节剂和治疗受损肝的新治疗靶标。

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