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Disturbances in metabolic, transport and structural genes in experimental colonic inflammation in the rat: a longitudinal genomic analysis.

Martínez-Augustin O, Merlos M, Zarzuelo A, Suárez MD, de Medina FS - BMC Genomics (2008)

Bottom Line: They were related to a number of biological functions, not only inflammation/immunity but also transport, metabolism, signal transduction, tissue remodeling and angiogenesis.The results were successfully validated in a subset of genes by real-time PCR.The changes observed correlate with pathophysiological disturbances such as tissue remodelling and alterations in ion transport, which are characteristic of both this model and IBD.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biochemistry and Molecular Biology II, CIBEREHD, School of Pharmacy, University of Granada, Granada, Spain. omartine@ugr.es

ABSTRACT

Background: Trinitrobenzenesulphonic acid (TNBS) induced rat colitis is one of the most widely used models of inflammatory bowel disease (IBD), a condition whose aetiology and pathophysiology are incompletely understood. We have characterized this model at the genomic level using a longitudinal approach. Six control rats were compared with colitic animals at 2, 5, 7 and 14 days after TNBS administration (n = 3). The Affymetrix Rat Expression Array 230 2.0 system was used.

Results: TNBS-induced colitis had a profound impact on the gene expression profile, which was maximal 5 and 7 days post-induction. Most genes were affected at more than one time point. They were related to a number of biological functions, not only inflammation/immunity but also transport, metabolism, signal transduction, tissue remodeling and angiogenesis. Gene changes generally correlated with the severity of colitis. The results were successfully validated in a subset of genes by real-time PCR.

Conclusion: The TNBS model of rat colitis has been described in detail at the transcriptome level. The changes observed correlate with pathophysiological disturbances such as tissue remodelling and alterations in ion transport, which are characteristic of both this model and IBD.

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Related in: MedlinePlus

Behaviour over time of genes involved in metabolism. Upregulated genes are shown in red and downregulated genes in blue. Gene expression was considered significantly changed by inflammation at p < 0.05 after analysis of variance followed by Tukey post-hoc tests and Benjamini & Hochberg false discovery rate correction.
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Figure 6: Behaviour over time of genes involved in metabolism. Upregulated genes are shown in red and downregulated genes in blue. Gene expression was considered significantly changed by inflammation at p < 0.05 after analysis of variance followed by Tukey post-hoc tests and Benjamini & Hochberg false discovery rate correction.

Mentions: Metabolism-related genes were highly affected (mostly decreased) by TNBS-induced colitis (Fig. 6 and also Fig. 7 for validated genes). They included genes participating in glycolysis, like Aldob and many different subunits of the pyruvate dehydrogenase complex (Dlat, Dld, Pdha1, Pdhb). Several enzymes of the Krebs cycle were also changed, e.g., Idh3g, Aco2, Sucla2 and Cs. The respiratory chain genes Ndufs1 and Sdhc and several genes encoding cytochrome isoforms were also downregulated.


Disturbances in metabolic, transport and structural genes in experimental colonic inflammation in the rat: a longitudinal genomic analysis.

Martínez-Augustin O, Merlos M, Zarzuelo A, Suárez MD, de Medina FS - BMC Genomics (2008)

Behaviour over time of genes involved in metabolism. Upregulated genes are shown in red and downregulated genes in blue. Gene expression was considered significantly changed by inflammation at p < 0.05 after analysis of variance followed by Tukey post-hoc tests and Benjamini & Hochberg false discovery rate correction.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2577662&req=5

Figure 6: Behaviour over time of genes involved in metabolism. Upregulated genes are shown in red and downregulated genes in blue. Gene expression was considered significantly changed by inflammation at p < 0.05 after analysis of variance followed by Tukey post-hoc tests and Benjamini & Hochberg false discovery rate correction.
Mentions: Metabolism-related genes were highly affected (mostly decreased) by TNBS-induced colitis (Fig. 6 and also Fig. 7 for validated genes). They included genes participating in glycolysis, like Aldob and many different subunits of the pyruvate dehydrogenase complex (Dlat, Dld, Pdha1, Pdhb). Several enzymes of the Krebs cycle were also changed, e.g., Idh3g, Aco2, Sucla2 and Cs. The respiratory chain genes Ndufs1 and Sdhc and several genes encoding cytochrome isoforms were also downregulated.

Bottom Line: They were related to a number of biological functions, not only inflammation/immunity but also transport, metabolism, signal transduction, tissue remodeling and angiogenesis.The results were successfully validated in a subset of genes by real-time PCR.The changes observed correlate with pathophysiological disturbances such as tissue remodelling and alterations in ion transport, which are characteristic of both this model and IBD.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biochemistry and Molecular Biology II, CIBEREHD, School of Pharmacy, University of Granada, Granada, Spain. omartine@ugr.es

ABSTRACT

Background: Trinitrobenzenesulphonic acid (TNBS) induced rat colitis is one of the most widely used models of inflammatory bowel disease (IBD), a condition whose aetiology and pathophysiology are incompletely understood. We have characterized this model at the genomic level using a longitudinal approach. Six control rats were compared with colitic animals at 2, 5, 7 and 14 days after TNBS administration (n = 3). The Affymetrix Rat Expression Array 230 2.0 system was used.

Results: TNBS-induced colitis had a profound impact on the gene expression profile, which was maximal 5 and 7 days post-induction. Most genes were affected at more than one time point. They were related to a number of biological functions, not only inflammation/immunity but also transport, metabolism, signal transduction, tissue remodeling and angiogenesis. Gene changes generally correlated with the severity of colitis. The results were successfully validated in a subset of genes by real-time PCR.

Conclusion: The TNBS model of rat colitis has been described in detail at the transcriptome level. The changes observed correlate with pathophysiological disturbances such as tissue remodelling and alterations in ion transport, which are characteristic of both this model and IBD.

Show MeSH
Related in: MedlinePlus