Identification of gene signatures for prednisolone-induced metabolic dysfunction in collagen-induced arthritic mice
Sandrine Ellero-Simatos1, Wilco W M Fleuren, Susanne Bauerschmidt
1Division Analytical Biosciences, Leiden Academic Centre for Drug Research, Leiden, The Netherlands.
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.
