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| Status |
Public on Sep 05, 2013 |
| Title |
Transcriptional Profiling Defines the Roles of ERK and p38 Kinases in Epidermal Keratinocytes |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Epidermal keratinocytes respond to extracellular influences by activating cytoplasmic signal transduction pathways that change the transcriptional profiles of affected cells. To define responses to two such pathways, p38 and ERK, we used SB203580 and PD98059 as specific inhibitors, and identified the regulated genes after 1, 4, 24 and 48 hrs, using Affymetrix’ Hu133Av2 microarrays. Additionally, we compared genes specifically regulated by p38 and ERKs with those regulated by JNK and by all three pathways simultaneously. We find that the p38 pathway induces the expression of extracellular matrix and proliferation-associated genes, while suppressing microtubule-associated genes; the ERK pathway induces the expression of nuclear envelope and mRNA splicing proteins, while suppressing steroid synthesis and mitochondrial energy production enzymes. Both pathways promote epidermal differentiation and induce feedback inactivation of MAPK signaling. c-FOS, SRY and N-Myc appear to be the principal targets of the p38 pathway, Elk-1 SAP1 and HLH2 of ERK, while FREAC-4, ARNT and USF are common to both. The results for the first time comprehensively define the genes regulated by the p38 and ERK pathways in epidermal keratinocytes and suggest a list of targets potentially useful in therapeutic interventions.
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| Overall design |
Human epidermal keratinocytes are grown in Keratinocyte Serum-Free Medium (Gibco) supplemented with 0.05 mg/ml bovine pituitary extract, 2.5 ng/ml epidermal growth factor, 0.09 mM CalCl2 and 1% penicillin/streptomycin (KGM). They are switched to Keratinocyte Serum Free-Media (Gibco) supplemented only with 1% penicillin/streptomycin (KBM) 24 h prior to commencing experiments. A set is left as controls, others treated with 5 uM JNK inhibitor SP600125, 15 uM p38 inhibitor SB203580, or 50 um ERK inhibitor PD98059. Timecourse of treated and parellel control samples over a 48 hr period was performed.
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| Contributor(s) |
Gazel A, Nijhawan RI, Walsh R, Blumenberg M |
| Citation(s) |
18247374 |
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| Submission date |
Sep 04, 2013 |
| Last update date |
Dec 06, 2018 |
| Contact name |
Miroslav Blumenberg |
| E-mail(s) |
[email protected]
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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) |
| GPL571 |
[HG-U133A_2] Affymetrix Human Genome U133A 2.0 Array |
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| Samples (16)
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| Relations |
| BioProject |
PRJNA218008 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE50591_RAW.tar |
26.8 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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