Gene modulation associated with inhibition of liver regeneration in hepatitis B virus X transgenic mice

摘要

AIM: To analyze the modulation of gene expression profi le associated with inhibition of liver regeneration in hepatitis B X (HBx)-expressing transgenic mice. METHODS: Microarray technology was performed on liver tissue obtained from 4 control (LacZ) and 4 transgenic mice (HBx-LacZ),48 h after partial hepatectomy. The significance of the normalized log-ratios was assessed for each gene,using robust t-tests under an empirical Bayes approach. Microarray hybridization data was verified on selected genes by quantitative PCR. RESULTS: The comparison of gene expression patterns showed a consistent modulation of the expression of 26 genes,most of which are implicated in liver regeneration. Up-regulated genes included DNA repair proteins (Rad-52,MSH6) and transmembrane proteins (syndecan 4,tetraspanin),while down-regulated genes were connected to the regulation of transcription (histone deacetylase,Zfp90,MyoD1) and were involved in the cholesterol metabolic pathway and isoprenoid biosynthesis (farnesyl diphosphate synthase,Cyp7b1,geranylgeranyl diphosphate synthase,SAA3). CONCLUSION: Our results provide a novel insight into the biological activities of HBx,implicated in the inhibition of liver regeneration.