Regulation of epithelial-mesenchymal IL-1 signaling by PPARbeta/delta is essential for skin homeostasis and wound healing.

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Serval ID
serval:BIB_B7E22B892AE6
Type
Article: article from journal or magazin.
Collection
Publications
Title
Regulation of epithelial-mesenchymal IL-1 signaling by PPARbeta/delta is essential for skin homeostasis and wound healing.
Journal
Journal of Cell Biology
Author(s)
Chong H.C., Tan M.J., Philippe V., Tan S.H., Tan C.K., Ku C.W., Goh Y.Y., Wahli W., Michalik L., Tan N.S.
ISSN
1540-8140[electronic]
Publication state
Published
Issued date
2009
Peer-reviewed
Oui
Volume
184
Number
6
Pages
817-831
Language
english
Abstract
Skin morphogenesis, maintenance, and healing after wounding require complex epithelial-mesenchymal interactions. In this study, we show that for skin homeostasis, interleukin-1 (IL-1) produced by keratinocytes activates peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) expression in underlying fibroblasts, which in turn inhibits the mitotic activity of keratinocytes via inhibition of the IL-1 signaling pathway. In fact, PPARbeta/delta stimulates production of the secreted IL-1 receptor antagonist, which leads to an autocrine decrease in IL-1 signaling pathways and consequently decreases production of secreted mitogenic factors by the fibroblasts. This fibroblast PPARbeta/delta regulation of the IL-1 signaling is required for proper wound healing and can regulate tumor as well as normal human keratinocyte cell proliferation. Together, these findings provide evidence for a novel homeostatic control of keratinocyte proliferation and differentiation mediated via PPARbeta/delta regulation in dermal fibroblasts of IL-1 signaling. Given the ubiquitous expression of PPARbeta/delta, other epithelial-mesenchymal interactions may also be regulated in a similar manner.
Keywords
Animals, Autocrine Communication, Cell Differentiation, Cell Proliferation, Cells, Cultured, Cytokines/metabolism, Epithelial Cells/enzymology, Epithelial Cells/immunology, Fibroblasts/enzymology, Fibroblasts/immunology, Gene Knockdown Techniques, Homeostasis, Humans, Intercellular Signaling Peptides and Proteins/metabolism, Interleukin 1 Receptor Antagonist Protein/genetics, Interleukin 1 Receptor Antagonist Protein/metabolism, Interleukin-1/genetics, Interleukin-1/metabolism, Interleukin-1alpha/metabolism, Interleukin-1beta/metabolism, MAP Kinase Kinase Kinases/metabolism, Mice, Mice, Knockout, Organ Culture Techniques, PPAR delta/deficiency, PPAR delta/genetics, PPAR-beta/deficiency, PPAR-beta/genetics, Paracrine Communication, Promoter Regions, Genetic, RNA Interference, Signal Transduction, Skin/enzymology, Skin/immunology, Time Factors, Transcription Factor AP-1/metabolism, Transcriptional Activation, Wound Healing
Pubmed
Web of science
Open Access
Yes
Create date
18/06/2009 15:28
Last modification date
20/08/2019 16:25
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