Regulation of epithelial–mesenchymal IL-1 signaling by PPARβ/δ is essential for skin homeostasis and wound healing
In: Journal of Cell Biology, Jg. 184 (2009-03-23), S. 817-831
Online
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Zugriff:
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.
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Regulation of epithelial–mesenchymal IL-1 signaling by PPARβ/δ is essential for skin homeostasis and wound healing
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Autor/in / Beteiligte Person: | Philippe, Virginie ; Chek Kun Tan ; Ming Jie Tan ; Yan Yih Goh ; Michalik, Liliane ; Nguan Soon Tan ; Siew Hwey Tan ; Wahli, Walter ; Chee Wai Ku ; Han Chung Chong |
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Zeitschrift: | Journal of Cell Biology, Jg. 184 (2009-03-23), S. 817-831 |
Veröffentlichung: | Rockefeller University Press, 2009 |
Medientyp: | unknown |
ISSN: | 1540-8140 (print) ; 0021-9525 (print) |
DOI: | 10.1083/jcb.200809028 |
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