title: The role of peroxisome proliferator-activated receptor-beta/delta in epidermal growth factor-induced HaCaT cell proliferation.
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-beta/delta (PPARbeta/delta) expression and activation is involved in the cell proliferation. However, little is known about the role of PPARbeta/delta 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 PPARbeta/delta mRNA and protein level expression in time-dependent and dose-dependent manner, and AG1487, an EGF receptor (EGFR) special inhibitor, caused attenuation of PPARbeta/delta protein expression. Electrophoretic mobility shift assay (EMSA) revealed that EGF significantly increased PPARbeta/delta binding activity in HaCaT keratinocytes. Antisense phosphorothioate oligonucleotides (asODNs) against PPARbeta/delta caused selectively inhibition of PPARbeta/delta protein content induced by EGF and significantly attenuated EGF-mediated cell proliferation. Treatment of the cells with L165041, a specific synthetic ligand for PPARbeta/delta, significantly enhanced EGF-mediated cell proliferation. Finally, c-Jun ablation inhibited PPARbeta/delta up-regulation induced by EGF, and chromatin immunoprecipitation (ChIP) showed that c-Jun bound to the PPARbeta/delta promoter and the binding increased in EGF-stimulated cells. These results demonstrate that EGF induces PPARbeta/delta expression in a c-Jun-dependent manner and PPARbeta/delta plays a vital role in EGF-stimulated proliferation of HaCaT cells.
authors.affiliation: Department of Burns and Plastic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, PR China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Liang
authors.forename: Bimei
authors.initials: B
authors.lastname: Jiang
authors.forename: Xinghua
authors.initials: X
authors.lastname: Yang
authors.forename: Xianzhong
authors.initials: X
authors.lastname: Xiao
authors.forename: Xu
authors.initials: X
authors.lastname: Huang
authors.forename: Jianhong
authors.initials: J
authors.lastname: Long
authors.forename: Pihong
authors.initials: P
authors.lastname: Zhang
authors.forename: Minghua
authors.initials: M
authors.lastname: Zhang
authors.forename: Muzhang
authors.initials: M
authors.lastname: Xiao
authors.forename: Tinghong
authors.initials: T
authors.lastname: Xie
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Huang
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005786:Gene Expression Regulation; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D047494:PPAR delta / Q000235:genetics / Q000378:metabolism*; D048068:PPAR-beta / Q000235:genetics / Q000378:metabolism*; D010642:Phenoxyacetates / Q000378:metabolism
chemical_list: C520164:4-(3-(2-propyl-3-hydroxy-4-acetyl)phenoxy)propyloxyphenoxy acetic acid; D016376:Oligonucleotides, Antisense; D047494:PPAR delta; D048068:PPAR-beta; D010642:Phenoxyacetates; D004815:Epidermal Growth Factor; D048031:JNK Mitogen-Activated Protein Kinases