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| Status |
Public on Jan 07, 2011 |
| Title |
Effects of Glucocorticoids in Epidermal Keratinocytes |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Glucocorticoids (GCs) have a long history of use as therapeutic agents for numerous skin diseases. Surprisingly, their specific molecular effects are largely unknown. To characterize GC action in epidermis, we compared the transcriptional profiles of primary human keratinocytes untreated and treated with dexamethasone (DEX) for 1, 4, 24, 48 and 72 hours using large-scale microarray analyses. The majority of genes were found regulated only after 24 hours and remained regulated throughout the treatment. In addition to expected anti-inflammatory genes, we found that GCs regulate cell fate, tissue remodeling, cell motility, differentiation and metabolism. GCs not only effectively block signaling by TNF-alpha and IL-1 but also by IFN-gamma, which was not previously known. Specifically, GCs suppress the expression of essentially all IFN-gamma-regulated genes, including IFN-gamma receptor and STAT-1. GCs also block STAT-1 activation and nuclear translocation. Unexpectedly, GCs have anti-apoptotic effects in keratinocytes by inducing the expression of anti-apoptotic and repressing pro-apoptotic genes. Consequently, GCs treatment blocked UV-induced apoptosis of keratinocytes. GCs have a profound effect on wound healing by inhibiting cell motility and the expression of pro-angiogenic factor VEGF. They play an important role in tissue remodeling and scar formation by suppressing the expression of TGF-beta-1 and -2, MMP1, 2, 9 and 10 and inducing TIMP-2. Finally, GCs promote terminal stages of epidermal differentiation while simultaneously inhibiting the early stages. These results provide new insights into the beneficial and adverse effects of GCs in epidermis, defining the participating genes and mechanisms that coordinate the cellular responses important for GC-based therapies.
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| Overall design |
Human epidermal keratinocytes are grown in delipidized, phenolphtalein-free medium and left as controls or treated with 0.1μM dexamethasone. Time course of treated and parallel control samples over a 72 hr period was performed twice with independent batches of cells.
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| Contributor(s) |
Stojadinovic O, Lee B, Vouthounis C, Vukelic S, Pastar I, Blumenberg M, Brem H, Tomic-Canic M |
| Citation(s) |
17095510 |
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| Submission date |
Jan 06, 2011 |
| Last update date |
Dec 13, 2018 |
| Contact name |
Miroslav Blumenberg |
| E-mail(s) |
miroslav.blumenberg@nyumc.org
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| Phone |
212 263-5924
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| Organization name |
NYU School of Medicine
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| Department |
Dermatology
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| Lab |
Blumenberg
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| Street address |
455 First Ave #874
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| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10016 |
| Country |
USA |
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| Platforms (1) |
| GPL8300 |
[HG_U95Av2] Affymetrix Human Genome U95 Version 2 Array |
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| Samples (20)
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| GSM651312 |
Keratinocytes, untreated 48h, rep1 |
| GSM651313 |
Keratinocytes, untreated 72h, rep1 |
| GSM651314 |
Keratinocytes, DEX-treated 1h, rep1 |
| GSM651315 |
Keratinocytes, DEX-treated 4h, rep1 |
| GSM651316 |
Keratinocytes, DEX-treated 24h, rep1 |
| GSM651317 |
Keratinocytes, DEX-treated 48h, rep1 |
| GSM651318 |
Keratinocytes, DEX-treated 72h, rep1 |
| GSM651319 |
Keratinocytes, untreated 1h, rep2 |
| GSM651320 |
Keratinocytes, untreated 4h, rep2 |
| GSM651321 |
Keratinocytes, untreated 24h, rep2 |
| GSM651322 |
Keratinocytes, untreated 48h, rep2 |
| GSM651323 |
Keratinocytes, untreated 72h, rep2 |
| GSM651324 |
Keratinocytes, DEX-treated 1h, rep2 |
| GSM651325 |
Keratinocytes, DEX-treated 4h, rep2 |
| GSM651326 |
Keratinocytes, DEX-treated 24h, rep2 |
| GSM651327 |
Keratinocytes, DEX-treated 48h, rep2 |
| GSM651328 |
Keratinocytes, DEX-treated 72h, rep2 |
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| Relations |
| BioProject |
PRJNA136485 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE26487_RAW.tar |
52.1 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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