Involvement of metastasis tumor antigen 1 in hepatic regeneration and proliferation
Involvement of metastasis tumor antigen 1 in hepatic regeneration and proliferation
复制标题
转移肿瘤抗原1参与肝再生和增殖
DOI：
10.1159/000149810
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发表时间：
2008-01-01
影响因子：
--
通讯作者：
Zhang, Yuanqiang
中科院分区：
文献类型：
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作者：
Li, Wei;Zhu, Huaping;Zhang, Yuanqiang
背景/目的：转移肿瘤抗原1(MTA1)是核小体重构和组蛋白去乙酰化(NuRD)复合体的组成部分，与转移潜能密切相关，能够通过改变关键靶基因的乙酰化状态来调节不同的细胞通路。然而，这种分子的其他生物学功能在很大程度上仍未被探索。本研究旨在探讨该分子在小鼠肝脏中的潜在作用。方法：首先在小鼠肝部分切除模型(PHX)中检测MTA1的表达。采用流体力学基因转移方法检测MTA1过表达对小鼠肝脏增殖和分化的影响，并用高表达MTA1的转化细胞系AML12进行体外实验。结果：与肝再生相一致，MTA1的表达在PHX后24小时显著升高，在PHX后48小时达到高峰。在PHX后，MTA1免疫反应性普遍升高，染色似乎经历了从胞浆到胞核的转变。外源性MTA1过表达在体内可显著刺激肝细胞增殖，在体外可促进肝细胞分化。结论：这些数据强调了这个最近定义的分子的一个肝细胞方面，它可能代表一个新的调节因子和一个新的治疗靶点，用于治疗受损的肝脏。
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.