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hhLIM参与胚胎干细胞的心肌生成过程。

hhLIM is involved in cardiomyogenesis of embryonic stem cells.

作者信息

Zheng Bin, Wen Jin-Kun, Han Mei

机构信息

Hebei Laboratory of Medical Biotechnology, Institute of Basic Medicine, Hebei Medical University, Shijiazhuang 050017, China.

出版信息

Biochemistry (Mosc). 2006;71 Suppl 1:S71-6, 6. doi: 10.1134/s0006297906130128.

Abstract

Proteins of the LIM family play important roles in a variety of fundamental biological processes including cell lineage specification and organ development. Here we examined the function in cardiogenesis of a new member of the LIM family, hhLIM, by molecular analysis of early stages of cardiomyocyte differentiation in hhLIM-deficient P19 cell line and P19 cells stably overexpressing hhLIM. The results indicate that hhLIM is a potent transcriptional activator of several cardiac muscle-specific genes. Inhibition of hhLIM expression by antisense transcripts can interfere with expression of cardiac muscle genes and block development of beating cardiomyocytes in P19 embryonic stem cells. Overexpression of hhLIM in P19 cells can enhance expression of cardiac marker genes Nkx2.5 and GATA-4 and potentiate development of cardiomyocyte-like morphology. These findings suggest that, in addition to its role in activation of the cardiac genetic program, hhLIM may be the nuclear target of inductive factor for precardiac cells.

摘要

LIM家族的蛋白质在包括细胞谱系特化和器官发育在内的多种基本生物学过程中发挥重要作用。在这里,我们通过对hhLIM缺陷型P19细胞系和稳定过表达hhLIM的P19细胞中心肌细胞分化早期阶段的分子分析,研究了LIM家族新成员hhLIM在心脏发生中的功能。结果表明,hhLIM是几种心肌特异性基因的有效转录激活因子。反义转录物抑制hhLIM表达可干扰心肌基因的表达,并阻断P19胚胎干细胞中跳动心肌细胞的发育。hhLIM在P19细胞中的过表达可增强心脏标志物基因Nkx2.5和GATA-4的表达,并促进心肌样形态的发育。这些发现表明,除了在激活心脏遗传程序中的作用外,hhLIM可能是心脏前体细胞诱导因子的核靶点。

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