Department of Hepatobiliary Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
Wound Repair Regen. 2010 Sep-Oct;18(5):524-31. doi: 10.1111/j.1524-475X.2010.00614.x.
Liver regeneration is a complex process that is orchestrated by the precise interplay of cell proliferation, differentiation control, and molecular pathways, but this complicated molecular signaling network is not fully understood. In this study, we showed that N-Myc downstream-regulated gene 2 (NDRG2) is involved in this process. The mRNA and protein levels of NDRG2 were strongly reduced when liver regeneration reached a peak of activity. In addition, we found that rat NDRG2 expression and C-Myc expression were inversely correlated during this process. A low level of NDRG2 was observed as the C-Myc expression increased during regeneration. Moreover, a dramatic cell cycle arrest was found in normal rat liver-derived BRL cells 48 hours after being infected by adenoviral vectors expressing rat NDRG2. Meanwhile, the apoptotic rates were increased from 9.4% in control group to 64.7% in adenoviral vectors expressing rat NDRG2 group. These phenomena could also be observed in BRL 3A and L-02 cells. Further analysis revealed that NDRG2 overexpression may mediate the antiproliferative effect by inducing p53 and p21 regulated Bax/Bcl-2 increase and cyclin E-Cdk2 inhibition. In conclusion, our findings point to physiological roles for NDRG2 in liver regeneration.
肝脏再生是一个复杂的过程，由细胞增殖、分化控制和分子途径的精确相互作用来协调，但这个复杂的分子信号网络尚未完全被理解。在这项研究中，我们表明 N- Myc 下游调节基因 2（NDRG2）参与了这一过程。当肝脏再生达到活动高峰时，NDRG2 的 mRNA 和蛋白水平明显降低。此外，我们发现大鼠 NDRG2 表达和 C-Myc 表达在这一过程中呈负相关。在再生过程中，随着 C-Myc 表达的增加，观察到 NDRG2 水平降低。此外，正常大鼠肝源性 BRL 细胞感染表达大鼠 NDRG2 的腺病毒载体 48 小时后，细胞周期明显停滞。同时，在腺病毒载体表达大鼠 NDRG2 组中，凋亡率从对照组的 9.4%增加到 64.7%。这些现象也可以在 BRL 3A 和 L-02 细胞中观察到。进一步分析表明，NDRG2 过表达可能通过诱导 p53 和 p21 调节的 Bax/Bcl-2 增加和细胞周期蛋白 E-Cdk2 抑制来介导抗增殖作用。总之，我们的发现表明 NDRG2 在肝脏再生中具有生理作用。
