Elsevier

Laboratory Investigation

Volume 91, Issue 2, February 2011, Pages 203-215
Laboratory Investigation

Research Article
DNA binding-dependent glucocorticoid receptor activity promotes adipogenesis via Krüppel-like factor 15 gene expression

https://doi.org/10.1038/labinvest.2010.170Get rights and content
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Abstract

Glucocorticoids, such as dexamethasone, have been used as in vitro inducers of adipogenesis. However, the roles of the glucocorticoid receptor (GR) in adipogenesis have not been well characterized yet. Here, we show that inhibition of GR activity using the GR antagonist RU486 prevents human mesenchymal stem cell and mouse embryonic fibroblast (MEF) differentiation into adipocytes. Moreover, in MEFs isolated from GR knockout (GRnull) and GRdim mice deficient in GR DNA-binding activity, adipogenesis was blocked. We identified glucocorticoid response element sites in the first intron of KLF15 by bioinformatical promoter analysis and confirmed their functional relevance by demonstrating GR interaction by chromatin immunoprecipitation. Moreover, transfection of MEFs with siRNA for KLF15 significantly attenuated the expressions of adipogenic-marker genes and the lipid accumulation. Our results provide a new mechanism for understanding glucocorticoids-dependent adipogenesis and that GR promotes adipogenesis via KLF15 gene expression as a transcriptional direct target.

KEYWORDS

adipogenesis
bioinformatics analysis
glucocorticoid receptor
human mesenchymal stem cell
Krüppel-like factor 15
mouse embryonic fibroblast

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Supplementary Information accompanies the paper on the Laboratory Investigation website

Maki Asada and Alexander Rauch: These authors contributed equally to this work.

Jan Tuckermann and Hiroshi Asahara: These authors contributed equally to this work.

Supplementary information The online version of this article (doi:10.1038/labinvest.2010.170) contains supplementary material, which is available to authorized users.