Liang Pengfei, Jiang Bimei, Huang Xu, Xiao Weimin, Zhang Pihong, Yang Xinghua, Long Jianhong, Xiao Xianzhong, Huang Xiaoyuan
Department of Burns and Plastic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Wound Repair Regen. 2008 Sep-Oct;16(5):691-8. doi: 10.1111/j.1524-475X.2008.00419.x.
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.
表皮生长因子（EGF）在上皮细胞增殖和凋亡中起重要作用。我们最近的研究发现，EGF可减轻肿瘤坏死因子-α诱导的HaCaT角质形成细胞凋亡，且这一效应伴随着过氧化物酶体增殖物激活受体β（PPARβ）表达的上调。然而，关于PPARβ是否在功能上参与EGF对角质形成细胞凋亡的抑制作用，目前知之甚少。在此，我们表明EGF上调了PPARβ的DNA结合和转录调控活性。针对PPARβ的反义硫代磷酸酯寡核苷酸显著抑制了PPARβ的从头合成，并减弱了EGF对肿瘤坏死因子-α诱导的凋亡的保护作用。L165041，一种特异性PPARβ配体，显著增强了PPARβ的转录调控活性，并增强了EGF的保护作用。这些结果提示了一种分子机制，即EGF以PPARβ依赖的方式保护HaCaT角质形成细胞免受凋亡。
