Unknown,Transcriptomics,Genomics,Proteomics

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Divergent genome expression profiles during hepatic ischemia in young and adult mice

ABSTRACT: Experimental Design: 1. The goal of the experiment: Age-Related Genome Expression Profiles During Hepatic Ischemia 2. Brief description of the experiment: Hepatic ischemia/reperfusion (I/R) injury is a complication of liver surgery, transplantation and shock and differs with age. In the present study, we sought to determine if the age-dependent response to I/R injury was related to differential gene expression during the ischemic period. Total RNA of young (4-5 weeks) and adult (12-14 months) mice undergoing sham surgery or partial hepatic ischemia for 30, 60, or 90 minutes was analyzed by 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. Significant differences in gene expression were observed between age groups. In young mice, 169 genes were down-regulated, whereas adult mice had 1167 genes down-regulated. Of these, only 28 genes were down-regulated in both young and adult mice. Far fewer genes had increased expression during ischemia. Sixty genes in young mice and 51 genes in adult mice were up-regulated. Of those, none were up-regulated in both young and adult mice. There were no distinct functional patterns of gene regulation in either age group. The data demonstrate significant and widespread changes in hepatic gene expression during the ischemic period that may be important to the age-dependent response to I/R injury. Keywords: treated vs non treated 2 age groups of 12 young and 12 adult mice that underwent either 30, 60 or 90 minutes of partial ischemia (n=3) or sham operation (n=3) We used microarray to uncover the genomic response during different time points of ischemia

ORGANISM(S): Mus musculus

SUBMITTER: Rebecca Schuster

PROVIDER: E-GEOD-10652 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Age-related decrease in proteasome expression contributes to defective nuclear factor-kappaB activation during hepatic ischemia/reperfusion.

Huber Nadine N Sakai Nozomu N Eismann Thorsten T Shin Thomas T Kuboki Satoshi S Blanchard John J Schuster Rebecca R Edwards Michael J MJ Wong Hector R HR Lentsch Alex B AB

Hepatology (Baltimore, Md.) 20090501 5

Hepatic ischemia/reperfusion (I/R) leads to liver injury and dysfunction through the initiation of a biphasic inflammatory response that is regulated by the transcription factor nuclear factor kappaB (NF-kappaB). We have previously shown that there is an age-dependent difference in the injury response to hepatic I/R in mice that correlates with divergent activation of NF-kappaB such that young mice have greater NF-kappaB activation, but less injury than old mice. In this study, we investigated t ...[more]

PMID: 19206148

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Project description: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

Dataset Information

Divergent genome expression profiles during hepatic ischemia in young and adult mice

Publications

Age-related decrease in proteasome expression contributes to defective nuclear factor-kappaB activation during hepatic ischemia/reperfusion.

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