The role of peroxisome proliferator-activated receptor-beta/delta in epidermal growth factor-induced HaCaT cell proliferation |
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Authors: | Liang Pengfei Jiang Bimei Yang Xinghua Xiao Xianzhong Huang Xu Long Jianhong Zhang Pihong Zhang Minghua Xiao Muzhang Xie Tinghong Huang Xiaoyuan |
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Institution: | a Department of Burns and Plastic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, PR China b Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, 410078, PR China c Department of Hyperbaric Oxygen, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, PR China |
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Abstract: | Epidermal growth factor (EGF) has been shown to be a potent mitogen for epidermal cells both in vitro and in vivo, thus contributing to the development of an organism. It has recently become clear that peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) expression and activation is involved in the cell proliferation. However, little is known about the role of PPARβ/δ in EGF-induced proliferation of HaCaT keratinocytes. In this study, HaCaT cells were cultured in the presence and absence of EGF and we identified that EGF induced an increase of PPARβ/δ mRNA and protein level expression in time-dependent and dose-dependent manner, and AG1487, an EGF receptor (EGFR) special inhibitor, caused attenuation of PPARβ/δ protein expression. Electrophoretic mobility shift assay (EMSA) revealed that EGF significantly increased PPARβ/δ binding activity in HaCaT keratinocytes. Antisense phosphorothioate oligonucleotides (asODNs) against PPARβ/δ caused selectively inhibition of PPARβ/δ protein content induced by EGF and significantly attenuated EGF-mediated cell proliferation. Treatment of the cells with L165041, a specific synthetic ligand for PPARβ/δ, significantly enhanced EGF-mediated cell proliferation. Finally, c-Jun ablation inhibited PPARβ/δ up-regulation induced by EGF, and chromatin immunoprecipitation (ChIP) showed that c-Jun bound to the PPARβ/δ promoter and the binding increased in EGF-stimulated cells. These results demonstrate that EGF induces PPARβ/δ expression in a c-Jun-dependent manner and PPARβ/δ plays a vital role in EGF-stimulated proliferation of HaCaT cells. |
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Keywords: | Epidermal growth factor Peroxisome proliferator-activated receptor-β/δ HaCaT cells Cell proliferation |
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