title: NDRG2 in rat liver regeneration: role in proliferation and apoptosis.
abstract: 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.
authors.affiliation: Department of Hepatobiliary Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
authors.forename: Jiandong
authors.initials: J
authors.lastname: Yang
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Lin
authors.initials: L
authors.lastname: Wu
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Zhang
authors.forename: Tenglong
authors.initials: T
authors.lastname: Han
authors.forename: Hang
authors.initials: H
authors.lastname: Guo
authors.forename: Ning
authors.initials: N
authors.lastname: Jiang
authors.forename: Kaishan
authors.initials: K
authors.lastname: Tao
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Ti
authors.forename: Xinping
authors.initials: X
authors.lastname: Liu
authors.forename: Libo
authors.initials: L
authors.lastname: Yao
authors.forename: Kefeng
authors.initials: K
authors.lastname: Dou
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D002453:Cell Cycle; D002460:Cell Line; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006498:Hepatectomy; D022781:Hepatocytes / Q000378:metabolism*; D007150:Immunohistochemistry; D008099:Liver; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012313:RNA / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C507213:Ndrg2 protein, rat; D009419:Nerve Tissue Proteins; D012313:RNA