title: Anti-apoptotic role of EGF in HaCaT keratinocytes via a PPARbeta-dependent mechanism.
abstract: 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.
authors.affiliation: Department of Burns and Plastic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Liang
authors.forename: Bimei
authors.initials: B
authors.lastname: Jiang
authors.forename: Xu
authors.initials: X
authors.lastname: Huang
authors.forename: Weimin
authors.initials: W
authors.lastname: Xiao
authors.forename: Pihong
authors.initials: P
authors.lastname: Zhang
authors.forename: Xinghua
authors.initials: X
authors.lastname: Yang
authors.forename: Jianhong
authors.initials: J
authors.lastname: Long
authors.forename: Xianzhong
authors.initials: X
authors.lastname: Xiao
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Huang
mesh_terms: 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
chemical_list: D048068:PPAR-beta; D014409:Tumor Necrosis Factor-alpha; D004815:Epidermal Growth Factor