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Series GSE59151 Query DataSets for GSE59151
Status Public on Aug 01, 2014
Title REDD1 (regulated in development and DNA damage response 1) dissociates therapeutic and adverse effects of topical steroids in skin
Organism Mus musculus
Experiment type Expression profiling by array
Summary Even though cutaneous atrophy is the major adverse effect of topical glucocorticoids, its molecular mechanisms are poorly understood. We found that glucocorticoids strongly increased the expression of REDD1 (regulated in development and DNA damage response 1), a stress-inducible inhibitor of mTOR, in mouse and human epidermis. We found that REDD1 knockout animals are partially resistant to glucocorticoid-induced epidermal and subcutaneous adipose atrophy which correlated with the protection of CD34+ follicular epithelial stem cells as well as p63+ keratinocyte progenitors in REDD1 knockout epidermis during chronic steroid treatment. At the same time, REDD1 knockout did not affect anti- inflammatory effect of glucocorticoids, as evaluated by ear edema test. Expression profiling revealed that ~ 50% of the glucocorticoid receptor (GR) target genes were not activated in epidermis of REDD1 knockouts, however, the negative effect of glucocorticoids on gene expression was similar to that in w.t. animals. Overall, our findings reveal a novel pathway in GR activation by its target gene/protein REDD1; and indicate an important role of REDD1 in glucocorticoid-induced skin atrophy, and maintenance of the epidermis and subcutaneous adipose. In addition, our findings form the foundation for the development of safer topical glucocorticoid treatment regimens by combining this therapy with REDD1 inhibitors.
 
Overall design Seven wk old B6D2 females in the telogen stage of the hair cycle were shaved, and treated 3 days later. Glucocorticoid FA was applied topically (2 ug/animal) in 200 ul acetone to the back skin once or up to four applications every third day as described previously (Chebotaev et al., 2007b). Control animals were treated with acetone only. Skin was harvested 24 h after last FA application or 4-8 h after single FA application as indicated in Figure legends. To evaluate the anti-inflammatory effect of glucocorticoid FA in REDD1 KO and w.t. B6x129 mice, we used ear edema test (Schoepe et al., 2010; Sch├Ącke et al., 2004; Park et al., 2006). Seven wk old female animals were pretreated with FA or vehicle applied to the back of the ear lobe one h before application of nonspecific contact irritant croton oil . Mice were sacrificed and ears were harvested nine hours after CO application, the time point at which we observed maximum ear edema in F1 C57Bl x 129 animals (data not shown). Four mm ear punch biopsies were immediately weighted to assess ear edema. Animals were injected i.p. with bromodeoxyuridine 1 hr before skin was harvested. Total RNA from murine epidermis and whole human skin was isolated with RiboPure kit (Ambion). Total RNA from murine s.c. adipose was isolated with RNeasy Lipid Tissue Kit (Qiagen). The RNA samples were treated with TURBOTM DNase (Ambion). Purity of RNA samples isolated from epidermis and s.c. fat was confirmed by the expression of adipose and keratinocyte cell markers.
 
Contributor(s) Budunova I
Citation(s) 25504525
Submission date Jul 07, 2014
Last update date Jun 14, 2018
Contact name Ben Readhead
E-mail(s) ben.readhead@asu.edu
Organization name ASU-Banner Neurodegenerative Disease Research Center
Street address 797 E. Tyler Street
City Tempe
State/province AZ
ZIP/Postal code 85281
Country USA
 
Platforms (1)
GPL6885 Illumina MouseRef-8 v2.0 expression beadchip
Samples (8)
GSM1429429 epidermis_wildtype_1
GSM1429430 epidermis_wildtype_2
GSM1429431 epidermis_wildtype_treated_FA_1
Relations
BioProject PRJNA254515

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE59151_RAW.tar 3.1 Mb (http)(custom) TAR
GSE59151_non-normalized.txt.gz 1.4 Mb (ftp)(http) TXT
Raw data are available on Series record
Processed data included within Sample table

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