Division Analytical Biosciences, Leiden Academic Centre for Drug Research, Leiden, The Netherlands.
Pharmacogenomics. 2014 Apr;15(5):629-41. doi: 10.2217/pgs.14.3.
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.
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.
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.
The identified gene signatures may provide useful starting points for the development of GCs with a better safety profile.
泼尼松龙是一种强效的抗炎糖皮质激素（GC），但由于代谢副作用，其长期使用受到阻碍。关于 GC 在炎症过程中对体内基因表达的长期影响知之甚少。
在长期治疗后，在复杂的体内炎症环境中，确定泼尼松龙诱导的代谢副作用相关的基因特征。
我们对关节炎和非关节炎小鼠进行了数种剂量的泼尼松龙治疗 3 周后的肝脏和肌肉的全基因组表达谱分析，并使用文本挖掘将基因特征与代谢途径联系起来。
泼尼松龙诱导的基因特征具有高度的组织特异性。我们确定了一个短名单的基因，这些基因受泼尼松龙和炎症的双重影响，与葡萄糖和脂肪酸代谢有关。对于其中的几个基因，GC 的关联是新颖的。
所确定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。
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