CSX/Nkx2.5 modulates differentiation of skeletal myoblasts and promotes differentiation into neuronal cells in vitro

CSX/Nkx2.5 modulates differentiation of skeletal myoblasts and promotes differentiation into neuronal cells in vitro
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DOI:
10.1074/jbc.m500028200
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发表时间:
2005-03-18
影响因子:
4.8
通讯作者:
Van Arsdell, G
Van Arsdell, G
中科院分区:
生物学2区
文献类型:
--
作者:
Riazi, AM;Lee, HY;Van Arsdell, G

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CSX/Nkx2.5转录因子在心脏发育中起关键作用;然而,它在其他器官的发育和分化中的作用尚未被研究。本研究以C2C12成肌细胞和人胎原代成肌细胞为研究对象,探讨Nkx2.5在骨骼肌发生中的功能。Nkx2.5的表达水平随着C2C12成肌细胞伸长融合形成肌管而降低。人NKX2.5在C2C12成肌细胞中的表达抑制了肌细胞分化和肌管的形成,上调了Gata4和Tbx5的表达。在终末分化的C2C12肌管中,NKX2.5的表达导致了肌管形态的改变并分解成更小的肌管。此外,NKX2.5在C2C12细胞和人胎儿成肌细胞原代培养物中过表达,导致成肌细胞向神经元样细胞分化,并表达神经元标记物。本研究揭示了Nkx2.5转录因子此前未知的非心脏功能。
CSX/Nkx2.5 transcription factor plays a pivotal role in cardiac development; however, its role in development and differentiation of other organs has not been investigated. In this study, we used C2C12 myoblasts and human fetal primary myoblasts to investigate the function of Nkx2.5 in skeletal myogenesis. The expression levels of Nkx2.5 decreased as C2C12 myoblasts elongated and fused to form myotubes. The expression of human NKX2.5 in C2C12 myoblasts inhibited myocyte differentiation and myotube formation, and up-regulated Gata4 and Tbx5 expression. The expression of NKX2.5 in terminally differentiated C2C12 myotubes resulted in a change in morphology and breakdown into smaller myotubes. Furthermore, overexpression of NKX2.5 in C2C12 cells and primary cultures of human fetal myoblasts led to differentiation of myoblasts into neuron-like cells and expression of neuronal markers. This study sheds light on the previously unknown non-cardiac functions of Nkx2.5 transcription factor.