TY - JOUR
T1 - Regulation of epithelial-mesenchymal IL-1 signaling by PPARβ/δ is essential for skin homeostasis and wound healing
AU - Chong, Han Chung
AU - Tan, Ming Jie
AU - Philippe, Virginie
AU - Tan, Siew Hwey
AU - Tan, Chek Kun
AU - Ku, Chee Wai
AU - Goh, Yan Yih
AU - Wahli, Walter
AU - Michalik, Liliane
AU - Tan, Nguan Soon
PY - 2009/3/23
Y1 - 2009/3/23
N2 - 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 keratino- cytes activates peroxisome proliferator-activated receptor (β/δ (PPAR β/δ) expression in underlying fibroblasts, which in turn inhibits the mitotic activity of keratinocytes via inhibition of the IL-1 signaling pathway. In fact, PPAR(β/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 PPAR(β/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 PPAR(β/δ regulation in dermal fibroblasts of IL-1 signaling. Given the ubiquitous expression of PPAR(β/δ, other epithelial- mesenchymal interactions may also be regulated in a similar manner.
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 keratino- cytes activates peroxisome proliferator-activated receptor (β/δ (PPAR β/δ) expression in underlying fibroblasts, which in turn inhibits the mitotic activity of keratinocytes via inhibition of the IL-1 signaling pathway. In fact, PPAR(β/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 PPAR(β/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 PPAR(β/δ regulation in dermal fibroblasts of IL-1 signaling. Given the ubiquitous expression of PPAR(β/δ, other epithelial- mesenchymal interactions may also be regulated in a similar manner.
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U2 - 10.1083/jcb.200809028
DO - 10.1083/jcb.200809028
M3 - Article
C2 - 19307598
AN - SCOPUS:64049095625
SN - 0021-9525
VL - 184
SP - 817
EP - 831
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 6
ER -