Identification of gene signatures for prednisolone-induced metabolic dysfunction in collagen-induced arthritic mice
| Autor: | Erik J M Toonen, Susanne Bauerschmidt, Sandrine Ellero-Simatos, Wim H. A. Dokter, Wilco W. M. Fleuren |
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| Přispěvatelé: | Leiden Academic Centre for Drug Research (LACDR), Radboud University Medical Center [Nijmegen], OSTHUS GmbH, Partenaires INRAE, Synthon |
| Rok vydání: | 2014 |
| Předmět: |
Male
medicine.medical_specialty Prednisolone [SDV]Life Sciences [q-bio] Anti-Inflammatory Agents Gene Expression Inflammation Other Research Radboud Institute for Molecular Life Sciences [Radboudumc 0] Pharmacology Biology Transcriptome Mice chemistry.chemical_compound Metabolic Diseases In vivo Internal medicine Gene expression Genetics medicine Animals Fatty acid metabolism Arthritis Muscles Fatty Acids Collagen Diseases Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6] collagen-induced arthritis mouse model n glucocorticoids n insulin sensitivity n metabolic side effects n prednisolone n transcriptomics n whole-genome expression profiling 3. Good health Gene expression profiling Glucose Endocrinology Liver chemistry Mice Inbred CBA Molecular Medicine Chemical and Drug Induced Liver Injury medicine.symptom Glucocorticoid medicine.drug |
| Zdroj: | Pharmacogenomics, 15, 629-41 Pharmacogenomics Pharmacogenomics, Future Medicine, 2014, 15 (5), pp.629-641. ⟨10.2217/PGS.14.3⟩ Pharmacogenomics, 15, 5, pp. 629-41 |
| ISSN: | 1462-2416 1744-8042 |
| Popis: | Background: Prednisolone is a potent anti-inflammatory glucocorticoid (GC) but chronic use is hampered by metabolic side effects. Little is known about the long-term effects of GCs on gene-expression in vivo during inflammation. Aim: Identify gene signatures underlying prednisolone-induced metabolic side effects in a complex in vivo inflammatory setting after long-term treatment. Materials & methods: We performed whole-genome expression profiling in liver and muscle from arthritic and nonarthritic mice treated with several doses of prednisolone for 3 weeks and used text-mining to link gene signatures to metabolic pathways. Results: Prednisolone-induced gene signatures were highly tissue specific. We identified a short-list of genes significantly affected by both prednisolone and inflammation in liver and involved in glucose and fatty acid metabolism. For several of these genes the association with GCs is novel. Conclusion: The identified gene signatures may provide useful starting points for the development of GCs with a better safety profile. Original submitted 2 September 2013; Revision submitted 3 January 2014 |
| Databáze: | OpenAIRE |
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