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-a 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.