Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of rat liver samples from individuals subjected to burn injury or cecal ligation and puncture

ABSTRACT: The experimental design included three biological replicates for each of the three conditions: Sham-Sham, Sham-CLP and burn-CLP. Liver samples were collected from the rats and the total RNA was analyzed on a Affymetrix RAE230A chip. No technical replicates were included in the study

ORGANISM(S): Rattus norvegicus

DISEASE(S): normal

SUBMITTER: Muralikrishna Vemula

PROVIDER: E-GEOD-1781 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Contribution of gene expression to metabolic fluxes in hypermetabolic livers induced through burn injury and cecal ligation and puncture in rats.

Banta Scott S Vemula Murali M Yokoyama Tadaaki T Jayaraman Arul A Berthiaume François F Yarmush Martin L ML

Biotechnology and bioengineering 20070501 1

Severe injury activates many stress-related and inflammatory pathways that can lead to a systemic hypermetabolic state. Prior studies using perfused hypermetabolic rat livers have identified intrinsic metabolic flux changes that were not dependent upon the continual presence of elevated stress hormones and substrate loads. We investigated the hypothesis that such changes may be due to persistent alterations in gene expression. A systemic hypermetabolic response was induced in rats by applying a ...[more]

PMID: 17009336

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Project description:Background: We hypothesized that spleen microarray gene expression profiles analyzed with contemporary pathway analysis software would provide molecular pathways of interest and target genes that might help explain the affect of bcl-2 on improving survival during sepsis. Methods: Two mouse models of sepsis, cecal ligation and puncture and tracheal instillation of Pseudomonas aeruginosa, were tested in both wild-type mice and mice that overexpress bcl-2. Whole spleens were obtained 6 hours after septic injury. DNA microarray transcriptional profiles were obtained using the Affymetrix 430A GeneChip, containing 22,690 elements. Ingenuity Pathway Analysis software was used to construct hypothetical transcriptional networks that changed in response to sepsis and expression of the bcl-2 transgene. Results: A conservative approach was used wherein only changes induced by both abdominal and pulmonary sepsis were studied. At 6 hours, sepsis induced alterations in the abundance of hundreds of spleen genes, including a number of proinflammatory mediators (e.g., IL-6). These sepsis-induced alterations were blocked by expression of the bcl-2 transgene. Network analysis implicated a number of bcl-2-related apoptosis genes, including bcl2L11 (bim), bcl-2L2 (bcl-w), bmf, and mcl-1. Sepsis in bcl-2 transgenic animals resulted in alteration of RNA abundance for only a single gene, ceacam1. Conclusion: These findings are consistent with sepsis-induced alterations in the balance of pro- and anti-apoptotic transcriptional networks. In addition, our data suggest that the ability of bcl-2 overexpression to improve survival in sepsis in this model is related in part to prevention of sepsis-induced alterations in spleen transcriptional responses. Experiment Overall Design: To determine the splenic response in these lethal models of CLP and Pseudomonas pneumonia, microarray analysis was performed on each spleen harvested from wild-type animals 6 hours after CLP or tracheal instillation of bacteria. The responses of the CLP or Pseudomonas spleens were compared concurrently to those of the wild-type controls, sham laparotomy and tracheal instillation of saline, respectively. This study was repeated in animals overexpressing bcl-2. Thus, the splenocyte effect of sepsis secondary to CLP (n=6) or Pseudomonas pneumonia (n=5) could be determined compared to their controls (n=6 and 5, respectively), and the effect of bcl-2 overexpression in turn also could be determined in both CLP (n=5) and pneumonia models (n=5) compared to controls (n=5 and 5, respectively).

Dataset Information

Transcription profiling of rat liver samples from individuals subjected to burn injury or cecal ligation and puncture

Publications

Contribution of gene expression to metabolic fluxes in hypermetabolic livers induced through burn injury and cecal ligation and puncture in rats.

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