The role of peroxisome proliferator-activated receptor-beta/delta in epidermal growth factor-induced HaCaT cell proliferation.
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.
Liang
Pengfei
P
Department of Burns and Plastic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, PR China.
Jiang
Bimei
B
Yang
Xinghua
X
Xiao
Xianzhong
X
Huang
Xu
X
Long
Jianhong
J
Zhang
Pihong
P
Zhang
Minghua
M
Xiao
Muzhang
M
Xie
Tinghong
T
Huang
Xiaoyuan
X
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
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