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Journal of Zhejiang University SCIENCE B 2012 Vol.13 No.9 P.695-706

http://doi.org/10.1631/jzus.B1100362


Impairment of liver regeneration by the histone deacetylase inhibitor valproic acid in mice


Author(s):  Qi Ke, Rui-na Yang, Feng Ye, Yu-jia Wang, Qiong Wu, Li Li, Hong Bu

Affiliation(s):  Department of Pathology, West China Hospital, Sichuan University, Chengdu 610041, China; more

Corresponding email(s):   hongbu@scu.edu.cn

Key Words:  Liver regeneration, Epigenetic factors, Cell cycle, VPA, B-myc


Qi Ke, Rui-na Yang, Feng Ye, Yu-jia Wang, Qiong Wu, Li Li, Hong Bu. Impairment of liver regeneration by the histone deacetylase inhibitor valproic acid in mice[J]. Journal of Zhejiang University Science B, 2012, 13(9): 695-706.

@article{title="Impairment of liver regeneration by the histone deacetylase inhibitor valproic acid in mice",
author="Qi Ke, Rui-na Yang, Feng Ye, Yu-jia Wang, Qiong Wu, Li Li, Hong Bu",
journal="Journal of Zhejiang University Science B",
volume="13",
number="9",
pages="695-706",
year="2012",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1100362"
}

%0 Journal Article
%T Impairment of liver regeneration by the histone deacetylase inhibitor valproic acid in mice
%A Qi Ke
%A Rui-na Yang
%A Feng Ye
%A Yu-jia Wang
%A Qiong Wu
%A Li Li
%A Hong Bu
%J Journal of Zhejiang University SCIENCE B
%V 13
%N 9
%P 695-706
%@ 1673-1581
%D 2012
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1100362

TY - JOUR
T1 - Impairment of liver regeneration by the histone deacetylase inhibitor valproic acid in mice
A1 - Qi Ke
A1 - Rui-na Yang
A1 - Feng Ye
A1 - Yu-jia Wang
A1 - Qiong Wu
A1 - Li Li
A1 - Hong Bu
J0 - Journal of Zhejiang University Science B
VL - 13
IS - 9
SP - 695
EP - 706
%@ 1673-1581
Y1 - 2012
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1100362


Abstract: 
Background and objective: liver regeneration is a complex process regulated by a group of genetic and epigenetic factors. A variety of genetic factors have been reported, whereas few investigations have focused on epigenetic regulation during liver regeneration. In the present study, valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, was used to investigate the effect of HDAC on liver regeneration. Methods: VPA was administered via intraperitoneal injection to 2/3 partially hepatectomized mice to detect hepatocyte proliferation during liver regeneration. The mice were sacrificed, and their liver tissues were harvested at sequential time points from 0 to 168 h after treatment. DNA synthesis was detected via a BrdU assay, and cell proliferation was tested using Ki-67. The expressions of cyclin D1, cyclin E, cyclin dependent kinase 2 (CDK2), and CDK4 were detected by Western blot analysis. Chromatin immunoprecipitation (ChIP) assay was used to examine the recruitment of HDACs to the target promoter regions and the expression of the target gene was detected by Western blot. Results: Immunohistochemical analysis showed that cells positive for BrdU and Ki-67 decreased, and the peak of BrdU was delayed in the VPA-administered mice. Consistently, cyclin D1 expression was also delayed. We identified b-myc as a target gene of HDACs by complementary DNA (cDNA) microarray. The expression of b-myc increased in the VPA-administered mice after hepatectomy (PH). The ChIP assay confirmed the presence of HDACs at the b-myc promoter. Conclusions: HDAC activities are essential for liver regeneration. Inhibiting HDAC activities delays liver regeneration and induces liver cell cycle arrest, thereby causing an anti-proliferative effect on liver regeneration.

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

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