Age-dependent gene expression profiles after hepatic ischemia/reperfusion in mice

ABSTRACT: Experimental Design: 1. The goal of the experiment: Age-Dependent Gene Expression Profiles After Hepatic Ischemia/Reperfusion: Implications for the AP-1 and Ubiquitin-Proteosome Pathways 2. Brief description of the experiment: Hepatic ischemia/reperfusion (I/R) injury is a complication of liver surgery, transplantation and shock. Our previous studies have suggested there is an age-dependent response to I/R. In the present study, we examined global gene expression after liver I/R in young (4-5 weeks) and adult (12-14 months) mice using Affymetrix microarray. Gene expression was filtered based on a change in expression of 1.5-fold relative to respective controls and then analyzed by ANOVA. Seventy-two genes in young mice and 56 genes in adult mice had significantly increased expression. Of these, only 18 were up-regulated in both age groups. In young mice, 289 genes were down-regulated whereas in adult mice, 874 genes were decreased. Of these genes, 175 genes were decreased in both groups. Pathway and network analyses of up- and down-regulated gene lists revealed a number of notable differences between young and adult mice. Of these, we found that genes related to the activating protein-1 (AP-1) pathway were upregulated preferentially in young mice. This corresponded with an increase in AP-1 activation in young versus adult mice. Finally, we found that genes related to the ubiquitin-proteasome pathway were selectively down-regulated in adult mice. This was accompanied by reduced degradation of the inhibitory protein, I?B?, in adult mice. The data demonstrate specific, pathway- and network-related differences in gene expression profiles between young and adult mice in the response to I/R. More specifically, we have identified two pathways that may contribute to the superior response to I/R in young mice which represent potential therapeutic targets. Keywords: treated vs non treated 2 age groups of 6 young and 6 adult mice that underwent either 90 minutes of partial ischemia followed by 1 hour of reperfusion (n=3) or sham operation (n=3) We used microarray to uncover the genomic response after ischemia reperfusion in 2 different age groups

ORGANISM(S): Mus musculus

SUBMITTER: Rebecca Schuster 

PROVIDER: E-GEOD-10654 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress