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Response of multiple genes to a chronic dose of corticosteroids in rat muscles

ABSTRACT: Synthetic glucocorticoids are used therapeutically for a variety of conditions. Both the efficacy and toxicity of corticosteroids arise from their pharmacologically exaggerated effects on target and non-target tissues. For example, beneficial effects deriving from inhibition of the immune system are accompanied by toxic side effects that include hyperglycemia, dyslipidaemia, muscle wasting, fatty liver, and an increased risk of atherosclerosis. Our previous time series analyzing the gene expression responses following a single bolus dose of methylprednisolone (MPL) provided interesting insight into the genomic responses of liver, skeletal muscle and kidney to corticosteroids. One objective with such extensive gene array time series data is to cluster genes into groups with common mechanisms of regulation. These clusters can be used to construct biologically rational models of the cascade of events that result in broad systemic phenomena such as diabetes, with the ultimate aim of therapeutic intervention at specific steps within the cascade Keywords: Time-Series

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE5101 | GEO | 2006/06/19

SECONDARY ACCESSION(S): PRJNA95357

REPOSITORIES: GEO

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Response of multiple genes to a chronic dose of corticosteroids in rat muscles

Project description:Synthetic glucocorticoids are used therapeutically for a variety of conditions. Both the efficacy and toxicity of corticosteroids arise from their pharmacologically exaggerated effects on target and non-target tissues. For example, beneficial effects deriving from inhibition of the immune system are accompanied by toxic side effects that include hyperglycemia, dyslipidaemia, muscle wasting, fatty liver, and an increased risk of atherosclerosis. Our previous time series analyzing the gene expression responses following a single bolus dose of methylprednisolone (MPL) provided interesting insight into the genomic responses of liver, skeletal muscle and kidney to corticosteroids. One objective with such extensive gene array time series data is to cluster genes into groups with common mechanisms of regulation. These clusters can be used to construct biologically rational models of the cascade of events that result in broad systemic phenomena such as diabetes, with the ultimate aim of therapeutic intervention at specific steps within the cascade Keywords: Time-Series We analyze the two time series profiles with the intent of seeking ways to use the two profiles in tandem for clustering. The acute profiles were generated by sacrificing animals following a single acute dose of MP [7]. The time points were: 0.25, 0.5, 0.75, 1, 2, 4, 5, 5.5, 6, 7, 8, 12, 18, 30, 48 and, 72 hours after dosing. The chronic profiles were generated by implanting Alzet mini-osmotic pumps with a constant flow rate [8, 9]. Animals were sacrificed at 6, 10, 13, 18, 24, 36, 48, 72, 96 and 168 hr following implantation.

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