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Series GSE4828

Query DataSets for GSE4828

Status

Public on May 16, 2006

Title

SP600125 effect on keratinocytes

Organism

Homo sapiens

Experiment type

Expression profiling by array

Summary

In inflamed tissue, normal signal transduction pathways are altered by extracellular signals. For example, the JNK pathway is activated in psoriatic skin, which makes it an attractive target for treatment. To define comprehensively the JNK-regulated genes in human epidermal keratinocytes, we compared the transcriptional profiles of control and JNK inhibitor-treated keratinocytes, using DNA microarrays. We identified the differentially expressed genes 1, 4, 24 and 48 hrs after the treatment with SP600125. Surprisingly, the inhibition of JNK in keratinocyte cultures in vitro induces virtually all aspects of epidermal differentiation in vivo: transcription of cornification markers, inhibition of motility, withdrawal from the cell cycle, stratification and even production of cornified envelopes. The inhibition of JNK also induces the production of enzymes of lipid and steroid metabolism, proteins of the diacylglycerol and inositol-phosphate pathways, mitochondrial proteins, histones and DNA repair enzymes, which have not been associated with differentiation previously. Simultaneously, basal cell markers, including integrins, hemidesmosome and ECM components, are suppressed. Promoter analysis of regulated genes finds that the binding sites for the forkhead family of transcription factors are over-represented in the SP600125-induced genes, and c-Fos sites in the suppressed genes. The JNK-induced proliferation appears to be secondary to inhibition of differentiation. The results indicate that the inhibition of JNK in epidermal keratinocytes is sufficient to initiate their differentiation program, and suggest that augmenting JNK activity could be used to delay cornification and enhance wound healing, while attenuating it could be a differentiation therapy-based approach for treating psoriasis.
Keywords: Time course. Inhibitor

Overall design

Keratinocytes are grown to ~75% confluence and either treated with 5nM SP600125, or left untreated. Samples are harvested 1, 4, 24 and 48hrs post-treatment.

Contributor(s)

Blumenberg M, Gazel A, Banno T, Walsh R

Citation(s)

16648634

Submission date

May 13, 2006

Last update date

Dec 13, 2018

Contact name

Miroslav Blumenberg

E-mail(s)

miroslav.blumenberg@nyumc.org