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- Title
PPARδ Enhances Keratinocyte Proliferation in Psoriasis and Induces Heparin-Binding EGF-Like Growth Factor.
- Authors
Romanowska, Malgorzata; al Yacoub, Nadya; Seidel, Henrik; Donandt, Susanne; Gerken, Hannah; Phillip, Sandra; Haritonova, Nathalie; Artuc, Metin; Schweiger, Susann; Sterry, Wolfram; Foerster, John
- Abstract
Psoriasis is a common skin disease involving keratinocyte proliferation and altered differentiation, as well as T-cell activation. Here, we show that altered gene transcription in psoriatic skin lesions is highly reproducible between independent data sets. Analysis of gene expression confirmed dysregulation in all expected functional categories, such as IFN signaling and keratinocyte differentiation, and allowed molecular fingerprinting of a previously characterized dendritic cell subset associated with psoriasis tumor necrosis factor alpha (TNF-α)- and inducible nitric oxide synthase (iNOS)-producing CD11bINT DC (Tip-DC). Unexpectedly, a large group of dysregulated transcripts was related to fatty acid signaling and adipocyte differentiation, exhibiting a pattern consistent with the activation of peroxisome proliferator-activated receptorδ (PPARδ). PPARδ itself was strongly induced in psoriasis in vivo. In primary keratinocytes, PPARδ was induced by the transcription factor activator protein 1, in particular by junB, but not by canonical WNT signaling, in contrast to its regulation in colon carcinoma cells. Activation of PPARδ enhanced proliferation of keratinocytes, while this was inhibited by knockdown of PPARδ. Finally, heparin-binding EGF-like growth factor (HB-EGF), known to induce epidermal hyperplasia and itself overexpressed in psoriasis, was identified as a direct target gene of PPARδ. The present data suggest that activation of PPARδ is a major event in psoriasis, contributing to the hyperproliferative phenotype by induction of HB-EGF.Journal of Investigative Dermatology (2008) 128, 110–124; doi:10.1038/sj.jid.5700943; published online 19 July 2007
- Subjects
PEROXISOMES; KERATINOCYTES; CELL proliferation; PSORIASIS; HEPARIN; EPIDERMAL growth factor; SKIN diseases; GENE expression
- Publication
Journal of Investigative Dermatology, 2008, Vol 128, Issue 1, p110
- ISSN
0022-202X
- Publication type
Article
- DOI
10.1038/sj.jid.5700943