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

Journal of Zhejiang University-Science b(biomedicine & biotechnology) 2012年第9期13卷 695-706页

作者： Qi KE Rui-na YANG Feng YE Yu-jia WANG QiongWU Li LI Hong bU Department of Pathology West China HospitalSichuan UniversityChengdu 610041China Department of Oncology the First Affiliated HospitalHenan University of Science and TechnologyLuoyang 471003China Key Laboratory of Transplant Engineering and Immunology of Ministry of Health West China HospitalSichuan UniversityChengdu 610041China

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 *** the present study,valproic acid(VPA),a histone deacetylase(HDAC) inhibitor,was used to investigate the effect of HDAC on liver ***:VPA was administered via intraperitoneal injection to 2/3 partially hepatectomized mice to detect hepatocyte proliferation during liver *** mice were sacrificed,and their liver tissues were harvested at sequential time points from 0 to 168 h after *** synthesis was detected via a brdU assay,and cell proliferation was tested using *** expressions of cyclin D1,cyclin E,cyclin dependent kinase 2(CDK2),and CDK4 were detected by Western blot *** 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 ***:Immunohistochemical analysis showed that cells positive for brdU and Ki-67 decreased,and the peak of brdU was delayed in the VPA-administered ***,cyclin D1 expression was also *** identified b-myc as a target gene of HDACs by complementary DNA(cDNA) *** 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 ***:HDAC activities are essential for liver *** HDAC activities delays liver regeneration and induces liver cell cycle arrest,thereby causing an anti-proliferative effect on liver regeneration.

关键词： Liver regeneration Epigenetic factors Cell cycle VPA b-myc

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