Anti-apoptotic role of EGF in HaCaT keratinocytes via a PPARβ-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 (PPAR beta). However, little is known about whether PPAR beta 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 PPAR beta. Antisense phosphorothioate oligonucleotides against PPAR beta markedly inhibited de novo synthesis of PPAR beta and attenuated the protective effect of EGF on tumor necrosis factor-alpha-induced apoptosis. L165041, a specific PPAR beta ligand, significantly enhanced the transcriptional regulation activity of PPAR beta and increased the protective effect of EGF. These results suggest a molecular mechanism by which EGF protects HaCaT keratinocytes against apoptosis in a PPAR beta-dependent manner.