Anti-apoptotic role of EGF in HaCaT keratinocytes via a PPARbeta-dependent mechanism.
Epidermal growth factor (EGF) plays an important role in epithelial cell proliferation and apoptosis. Our recent studies found that EGF-attenuated tumor necrosis factor-alpha induced HaCaT keratinocyte apoptosis, and this effect was accompanied by up-regulation of the expression of peroxisome proliferator-activated receptor beta (PPARbeta). However, little is known about whether PPARbeta is functionally involved in the inhibition of keratinocyte apoptosis by EGF. Here, we showed that EGF up-regulated the DNA-binding and transcriptional regulation activities of PPARbeta. Antisense phosphorothioate oligonucleotides against PPARbeta markedly inhibited de novo synthesis of PPARbeta and attenuated the protective effect of EGF on tumor necrosis factor-alpha-induced apoptosis. L165041, a specific PPARbeta ligand, significantly enhanced the transcriptional regulation activity of PPARbeta and increased the protective effect of EGF. These results suggest a molecular mechanism by which EGF protects HaCaT keratinocytes against apoptosis in a PPARbeta-dependent manner.
Liang
Pengfei
P
Department of Burns and Plastic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Jiang
Bimei
B
Huang
Xu
X
Xiao
Weimin
W
Zhang
Pihong
P
Yang
Xinghua
X
Long
Jianhong
J
Xiao
Xianzhong
X
Huang
Xiaoyuan
X
D017209:Apoptosis / Q000502:physiology*; D002460:Cell Line; D004815:Epidermal Growth Factor / Q000502:physiology*; D006801:Humans; D015603:Keratinocytes / Q000502:physiology*; D048068:PPAR-beta / Q000037:antagonists & inhibitors / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D015854:Up-Regulation
D048068:PPAR-beta; D014409:Tumor Necrosis Factor-alpha; D004815:Epidermal Growth Factor