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


CONCLUSIONS
Our results provide a novel insight into the biological activities of HBx, implicated in the inhibition of liver regeneration.
Sidorkiewicz
Malgorzata
M
INSERM (Institut National de la Sante et de la Recherche Medicale) U845, CHU Necker, 156 rue de Vaugirard, Paris 75015, France.
Jais
Jean-Philippe
JP
Tralhao
Guilherme
G
Morosan
Serban
S
Giannini
Carlo
C
Brezillon
Nicolas
N
Soussan
Patrick
P
Delpuech
Oona
O
Kremsdorf
Dina
D
D000818:Animals; D006498:Hepatectomy; D019694:Hepatitis B, Chronic / Q000235:genetics* / Q000503:physiopathology*; D007763:Lac Operon; D008115:Liver Regeneration / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D015534:Trans-Activators / Q000235:genetics*; D054334:Viral Regulatory and Accessory Proteins
D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein