The role of peroxisome proliferator-activated receptor-{beta}/{delta} in epidermal growth factor-induced HaCaT cell proliferation

Journal Article · Wed Oct 15 04:00:00 EDT 2008 · Experimental Cell Research

DOI:https://doi.org/10.1016/j.yexcr.2008.06.013· OSTI ID:21176127

Pengfei, Liang ^[1]; Bimei, Jiang ^[2]; Xinghua, Yang ^[1]; Xu, Huang ^[3]; Jianhong, Long; Pihong, Zhang; Minghua, Zhang; Muzhang, Xiao; Tinghong, Xie ^[1]

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1. Department of Burns and Plastic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, 410008 (China)
2. Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, 410078 (China)
3. Department of Hyperbaric Oxygen, Xiangya Hospital, Central South University, Changsha, Hunan, 410008 (China)

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} (PPAR{beta}/{delta}) expression and activation is involved in the cell proliferation. However, little is known about the role of PPAR{beta}/{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 PPAR{beta}/{delta} mRNA and protein level expression in time-dependent and dose-dependent manner, and AG1487, an EGF receptor (EGFR) special inhibitor, caused attenuation of PPAR{beta}/{delta} protein expression. Electrophoretic mobility shift assay (EMSA) revealed that EGF significantly increased PPAR{beta}/{delta} binding activity in HaCaT keratinocytes. Antisense phosphorothioate oligonucleotides (asODNs) against PPAR{beta}/{delta} caused selectively inhibition of PPAR{beta}/{delta} protein content induced by EGF and significantly attenuated EGF-mediated cell proliferation. Treatment of the cells with L165041, a specific synthetic ligand for PPAR{beta}/{delta}, significantly enhanced EGF-mediated cell proliferation. Finally, c-Jun ablation inhibited PPAR{beta}/{delta} up-regulation induced by EGF, and chromatin immunoprecipitation (ChIP) showed that c-Jun bound to the PPAR{beta}/{delta} promoter and the binding increased in EGF-stimulated cells. These results demonstrate that EGF induces PPAR{beta}/{delta} expression in a c-Jun-dependent manner and PPAR{beta}/{delta} plays a vital role in EGF-stimulated proliferation of HaCaT cells.

• OSTI ID: 21176127
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 17 Vol. 314; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ABLATION
ATTENUATION
CELL PROLIFERATION
CHROMATIN
ELECTROPHORESIS
GROWTH FACTORS
IN VITRO
IN VIVO
INHIBITION
LIGANDS
OLIGONUCLEOTIDES
RECEPTORS
TIME DEPENDENCE