Involvement of Metastasis Tumor Antigen 1 in Hepatic Regeneration and Proliferation

Abstract

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.