Comprehensive analysis of differential gene exrpession profiles on D-Galactosmaine-induced acute mouse liver injury and regeneration

Abstract

Microarray analysis of RNA from D-galactosamine-administered mouse livers was performed to establish a global gene expression profile during injury and regeneration stages at two different doses. A single dose of D-galactosamine (Gal-N) at 266 or 26.6 mg/kg body weight was given intraperitoneally, and the liver samples were obtained after 6, 24, and 72 h. Histopathologic studies enabled the classification of the D-galactosamine effect into injury (6, 24 h) and regeneration (72 h) stages. By using the Applied Biosystems Mouse Genome Survey Microarray, a total of 7,267 out of 33,012 (22.0%) genes were found to be statistically reliable at p < 0.05 by 2-way ANOVA, and 1,469 (4.4%) probes at false discovery rate < 5% by Significance Analysis of Microarray. Among the statistically reliable clones by both analytical methods, 401 genes were differentially expressed with more than a 1.625-fold difference (which equals 0.7 in log2 scale) at one or more Gal-N treatment conditions and with less than 1.625-fold difference at all three vehicle-treated conditions. Three hundred thirty seven genes and 15 genes were identified as injury- and regeneration-specific genes, respectively, showing that most of the transcriptomic changes were seen during the injury stage. Furthermore, multiple genes involved in oxidative stress, eicosanoid synthesis, apoptosis, and ATP synthesis showed variable transcript levels upon acute D-galactosamine administration.