Anti-apoptotic role of EGF in HaCaT keratinocytes via a PPARβ-dependent mechanism

• Published in: Wound repair and regeneration 2008-09, Vol.16 (5), p.691-698
• Main Authors: Liang, Pengfei, Jiang, Bimei, Huang, Xu, Xiao, Weimin, Zhang, Pihong, Yang, Xinghua, Long, Jianhong, Xiao, Xianzhong, Huang, Xiaoyuan
• Format: Article
• Language: English
• ISSN: 1067-1927; 1524-475X
• DOI: 10.1111/j.1524-475X.2008.00419.x

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‐α induced HaCaT keratinocyte apoptosis, and this effect was accompanied by up‐regulation of the expression of peroxisome proliferator‐activated receptor β (PPARβ). However, little is known about whether PPARβ 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 PPARβ. Antisense phosphorothioate oligonucleotides against PPARβ markedly inhibited de novo synthesis of PPARβ and attenuated the protective effect of EGF on tumor necrosis factor‐α–induced apoptosis. L165041, a specific PPARβ ligand, significantly enhanced the transcriptional regulation activity of PPARβ and increased the protective effect of EGF. These results suggest a molecular mechanism by which EGF protects HaCaT keratinocytes against apoptosis in a PPARβ‐dependent manner.