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World J Gastroenterol. Jan 28, 2008; 14(4): 574-581
Published online Jan 28, 2008. doi: 10.3748/wjg.14.574
Gene modulation associated with inhibition of liver regeneration in hepatitis B virus X transgenic mice
Malgorzata Sidorkiewicz, Jean-Philippe Jais, Guilherme Tralhao, Serban Morosan, Carlo Giannini, Nicolas Brezillon, Patrick Soussan, Oona Delpuech, Dina Kremsdorf
Malgorzata Sidorkiewicz, Guilherme Tralhao, Serban Morosan, Carlo Giannini, Nicolas Brezillon, Patrick Soussan, Oona Delpuech, Dina Kremsdorf, Inserm, U845, Paris 75015, France
Malgorzata Sidorkiewicz, Guilherme Tralhao, Serban Morosan, Carlo Giannini, Nicolas Brezillon, Patrick Soussan, Oona Delpuech, Dina Kremsdorf, Pasteur Institute, Department of Virology, Paris, France
Malgorzata Sidorkiewicz, Guilherme Tralhao, Serban Morosan, Carlo Giannini, Nicolas Brezillon, Patrick Soussan, Oona Delpuech, Dina Kremsdorf, University of Paris-Descartes, CHU Necker, Paris, France
Malgorzata Sidorkiewicz, Department of Medical Biochemistry, Medical University of Lodz, Lodz, Poland
Jean-Philippe Jais, Université Paris Descartes, CHU Necker, Service of Biostatistics and Medical Informatics, Paris, France
Carlo Giannini, Department of Internal Medicine, University of Florence, Florence, Italy
Correspondence to: Dina Kremsdorf, INSERM (Institut National de la Santé et de la Recherche Médicale) U845, CHU Necker; 156 rue de Vaugirard, Paris 75015, France. kremsdor@necker.fr
Telephone: +33-1-40615343
Fax: +33-1-40615581
Received: July 6, 2007
Revised: October 8, 2007
Published online: January 28, 2008
Abstract

AIM: To analyze the modulation of gene expression profile 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.

Keywords: Hepatitis B virus, Hepatitis B X (HBx) protein, Liver regeneration, Microarray analysis, Cholesterol, Isoprenoid