Project description:This SuperSeries is composed of the following subset Series: GSE10652: Divergent genome expression profiles during hepatic ischemia in young and adult mice GSE10654: Age-dependent gene expression profiles after hepatic ischemia/reperfusion in mice Keywords: SuperSeries Refer to individual Series
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
Project description: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
Project description: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
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
Project description:Purpose: to reveal the myocardium transcriptomic profile shift pattern before/after Ischemia Reperfusion stress in young, aged, and Sesn2-knockout mice. The goals of this study are to compare the transcriptomic shift pattern among young, aged, and Sesn2-knockout to explore the caridoprotective mechanism of Sesn2 in Ischemia Reperfusion stress and the critical roles of Sesn2 in age-related adapting response to Ischemia Reperfusion stress. Methods: Myocardium transcriptome profiles of young (3-4 months) wild-type, aged (24-26 months) wild-type, and Sesn2-knockout (3-4 months) mice in normal physiological and Ischemia Reperfusion stressed conditions. Results: Sesn2 is critical to repress inflammation and maintain metabolic and mitochondria homeostasis in hearts under Ischemia Reperfusion stress, especially to aged hearts.
Project description:To examine the age-related vulnerability to lung ischemia reperfusion injury, pulmonary gene expression profiles after lung ischemia reperfusion were compared between young and old mice.
Project description:Hepatic ischemia reperfusion injury is a dynamic process consisting of two stages: ischemia and reperfusion, and triggers a cascade of physiological and biochemical events. Given the important role of microRNAs in regulating gene expression, we analyzed gene expression changes in mouse livers at sham control, ischemia stage, and reperfusion stage. We generated global expression profiles of microRNA and mRNA genes in mouse livers subjected to ischemia reperfusion injury at the three stages, respectively. Comparison analysis showed that reperfusion injury had a distinct expression profile whereas the ischemia sample and the sham control were clustered together. Consistently, there are 69 differentially expressed microRNAs between the reperfusion sample and the sham control whereas 28 differentially expressed microRNAs between the ischemia sample and the sham control. We further identified two modes of microRNA expression changes in ischemia reperfusion injury. Functional analysis of both the differentially expressed microRNAs in the two modes and their target mRNAs revealed that ischemia injury impaired mitochondria function, nutrient consumption, and metabolism process. In contrast, reperfusion injury led to severe tissue inflammation that is predominantly an innate-immune response in the ischemia reperfusion process. Our staged analysis of gene expression profiles provides new insights into regulatory mechanisms of microRNAs in mouse hepatic ischemia reperfusion injury.
Project description:Ischemia/reperfusion injuries is a known complication to hepatic surgery. Ischemic pre- (IPC) and postconditioning (IPO) protects the liver against ischemia/reperfusion-injuries. Expression profiling were performed on liver biopsies seeking to identify molecular mediators of the protective properties. 48 rats were divided into 5 groups; sham (n=8), IRI (n=10), IPC (n=10), IPO (n=10) and IPC+IPO (n=10). All rats except sham rats were subjected to 30 min of total liver ischemia and 30 min of reperfusion before liver biopsies were sampled. In the IPC group, liver ischemia was preceded by 10 min of hepatic ischemia, followed by 10 min of reperfusion. IPO were performed by three cycles of 30 sec of reperfusion and 30 sec of ischemia, applied immediately after the 30 min of total liver ischemia. In the IPC+IPO group the two interventions were combined.
Project description:Hepatic ischemia reperfusion injury is a dynamic process consisting of two stages: ischemia and reperfusion, and triggers a cascade of physiological and biochemical events. Given the important role of microRNAs in regulating gene expression, we analyzed gene expression changes in mouse livers at sham control, ischemia stage, and reperfusion stage. We generated global expression profiles of microRNA and mRNA genes in mouse livers subjected to ischemia reperfusion injury at the three stages, respectively. Comparison analysis showed that reperfusion injury had a distinct expression profile whereas the ischemia sample and the sham control were clustered together. Consistently, there are 69 differentially expressed microRNAs between the reperfusion sample and the sham control whereas 28 differentially expressed microRNAs between the ischemia sample and the sham control. We further identified two modes of microRNA expression changes in ischemia reperfusion injury. Functional analysis of both the differentially expressed microRNAs in the two modes and their target mRNAs revealed that ischemia injury impaired mitochondria function, nutrient consumption, and metabolism process. In contrast, reperfusion injury led to severe tissue inflammation that is predominantly an innate-immune response in the ischemia reperfusion process. Our staged analysis of gene expression profiles provides new insights into regulatory mechanisms of microRNAs in mouse hepatic ischemia reperfusion injury.