NDRG2, a novel regulator of myoblast proliferation, is regulated by anabolic and catabolic factors
NDRG2, a novel regulator of myoblast proliferation, is regulated by anabolic and catabolic factors
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DOI：
10.1113/jphysiol.2008.167882
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发表时间：
2009-04-01
影响因子：
5.5
通讯作者：
Walder, Ken R.
中科院分区：
文献类型：
--
作者：
Foletta, Victoria C.;Prior, Matthew J.;Walder, Ken R.
骨骼肌组织经历适应性变化，以应对压力和基因控制这些过程是不完全的特点。NDRG 2（N-myc downstream-regulated gene 2）是一个应激和生长相关基因，本研究旨在探讨其在骨骼肌生长和适应中的作用。与未分化的成肌细胞相比，NDRG 2表达水平在分化的人和小鼠肌管中均被上调，而在C2 C12成肌细胞中抑制NDRG 2导致成肌细胞增殖减慢。细胞周期抑制剂p21 Waf 1/Cip 1和p27 Kip 1以及NDRG 2缺陷成肌细胞中各种肌肉分化标志物的表达水平增加表明，NDRG 2的缺乏促进了细胞周期退出和肌发生的开始。此外，在用分解代谢和合成代谢剂处理的C2 C12肌管中以及在抗阻运动训练后来自人类受试者的骨骼肌中的NDRG 2调节的分析揭示了NDRG 2基因表达在肥大条件期间下调，并且相反地，在肌肉萎缩期间上调。总之，这些数据表明，NDRG 2的表达是高度响应于骨骼肌中的不同应力条件，并表明NDRG 2的表达水平可能是成肌细胞的生长和分化的关键。
Skeletal muscle tissue undergoes adaptive changes in response to stress and the genes that control these processes are incompletely characterised. NDRG2 (N-myc downstream-regulated gene 2), a stress- and growth-related gene, was investigated in skeletal muscle growth and adaption. While NDRG2 expression levels were found to be up-regulated in both differentiated human and mouse myotubes compared with undifferentiated myoblasts, the suppression of NDRG2 in C2C12 myoblasts resulted in slowed myoblast proliferation. The increased expression levels of the cell cycle inhibitors, p21 Waf1/Cip1 and p27 Kip1, and of various muscle differentiation markers in NDRG2-deficient myoblasts indicate that a lack of NDRG2 promoted cell cycle exiting and the onset of myogenesis. Furthermore, the analysis of NDRG2 regulation in C2C12 myotubes treated with catabolic and anabolic agents and in skeletal muscle from human subjects following resistance exercise training revealed NDRG2 gene expression to be down-regulated during hypertrophic conditions, and conversely, up-regulated during muscle atrophy. Together, these data demonstrate that NDRG2 expression is highly responsive to different stress conditions in skeletal muscle and suggest that the level of NDRG2 expression may be critical to myoblast growth and differentiation.