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Identification of gene signatures for prednisolone-induced metabolic dysfunction in collagen-induced arthritic mice

机译:胶原诱导的关节炎小鼠中泼尼松龙诱导的代谢功能障碍的基因特征的鉴定

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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
机译:背景:泼尼松龙是一种有效的消炎性糖皮质激素(GC),但长期使用会受到代谢副作用的影响。关于GC对炎症过程中体内基因表达的长期影响知之甚少。目的:确定长期治疗后,在复杂的体内炎症环境中,泼尼松龙诱导的代谢副作用的潜在基因特征。材料和方法:我们对关节炎和非关节炎小鼠进行了3周全剂量全基因组表达谱分析,这些小鼠用泼尼松龙的不同剂量进行了3周的治疗,并通过文本挖掘将基因特征与代谢途径联系起来。结果:泼尼松龙诱导的基因签名具有高度组织特异性。我们确定了一个短名单的基因,这些基因受到泼尼松龙和肝脏炎症的影响,并参与葡萄糖和脂肪酸代谢。对于这些基因中的几种,与GC的关联是新颖的。结论:鉴定出的基因特征可能为开发具有更好安全性的GC提供有用的起点。原件于2013年9月2日提交;修订于2014年1月3日提交

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