Comprehensive analysis of differential gene expression profiles on carbon tetrachloride-induced rat liver injury and regeneration

Abstract

Microarray analysis of RNA from carbon tetrachloride (CCl 4)-administered rat livers was performed at various time points to establish a global gene expression profile during injury and regeneration stages. A single dose of 1 ml/kg of CCl 4 was given by ip injection, and the liver samples were obtained after 6, 24, 48 h, and 2 weeks. Histopathologic, biochemical, and immunohistochemical studies enabled the classification of the CCl 4 effect into injury (6 and 24 h) and regeneration (48 h and 2 weeks) stages. The expression levels of 5180 clones on a custom rat gene microarray were analyzed and 587 clones yielded changeable gene expression on at least single time point. One hundred seventy-nine clones were classified as injury-specific clones, while 38 clones as regeneration-specific clones. Characteristic gene expression profiles could be associated with CCl 4-induced gene expression with the disruption of lipid metabolism, which is known to cause the fatty liver induced by CCl 4 treatment. In addition, induction of the transcripts for many ribosomal proteins was detected during the injury stage, particularly at the 24-h time point, despite the previous report of decreased protein synthesis rate upon CCl 4 treatment. Several genes with known functions were also identified as CCl 4-regulated genes. In conclusion, we established a global gene expression profile utilizing microarray analysis in rat liver upon acute CCl 4 administration with a full chronological profile that not only covers injury stage but also later points of regeneration stage. © 2004 Elsevier Inc. All rights reserved.