RT Journal Article
SR Electronic
T1 Regulation of epithelial–mesenchymal IL-1 signaling by PPARβ/δ is essential for skin homeostasis and wound healing
JF The Journal of Cell Biology
JO J Cell Biol
FD Rockefeller University Press
SP 817
OP 831
DO 10.1083/jcb.200809028
VO 184
IS 6
A1 Chong, Han Chung
A1 Tan, Ming Jie
A1 Philippe, Virginie
A1 Tan, Siew Hwey
A1 Tan, Chek Kun
A1 Ku, Chee Wai
A1 Goh, Yan Yih
A1 Wahli, Walter
A1 Michalik, Liliane
A1 Tan, Nguan Soon
YR 2009
UL http://jcb.rupress.org/content/184/6/817.abstract
AB 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 β/δ (PPARβ/δ) expression in underlying fibroblasts, which in turn inhibits the mitotic activity of keratinocytes via inhibition of the IL-1 signaling pathway. In fact, PPARβ/δ 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 PPARβ/δ 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 PPARβ/δ regulation in dermal fibroblasts of IL-1 signaling. Given the ubiquitous expression of PPARβ/δ, other epithelial–mesenchymal interactions may also be regulated in a similar manner.