title: PPARbeta/delta selectively induces differentiation and inhibits cell proliferation.
abstract: Peroxisome proliferator-activated receptor (PPAR) beta-null mice exhibit exacerbated epithelial cell proliferation and enhanced sensitivity to skin carcinogenesis, suggesting that ligand activation of PPARbeta will inhibit keratinocyte proliferation. By using of a highly specific ligand (GW0742) and the PPARbeta-null mouse model, activation of PPARbeta was found to selectively induce keratinocyte terminal differentiation and inhibit keratinocyte proliferation. Additionally, GW0742 was found to be anti-inflammatory due to inhibition of myeloperoxidase activity, independent of PPARbeta. These data suggest that ligand activation of PPARbeta could be a novel approach to selectively induce differentiation and inhibit cell proliferation, thus representing a new molecular target for the treatment of skin disorders resulting from altered cell proliferation such as psoriasis and cancer.
authors: Department of Veterinary Science and The Center for Molecular Toxicology and Carcinogenesis, The Pennsylvania State University, University Park, PA 16802, USA.
authors: D J
authors: DJ
authors: Kim
authors: M T
authors: MT
authors: Bility
authors: A N
authors: AN
authors: Billin
authors: T M
authors: TM
authors: Willson
authors: F J
authors: FJ
authors: Gonzalez
authors: J M
authors: JM
authors: Peters
mesh_terms: D000818:Animals; D002118:Calcium / Q000494:pharmacology; D020013:Calcium Signaling; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D015603:Keratinocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D008024:Ligands; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D048068:PPAR-beta / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D009195:Peroxidase / Q000037:antagonists & inhibitors; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013844:Thiazoles / Q000378:metabolism / Q000494:pharmacology; D010636:Phenols; D013438:Sulfhydryl Compounds
chemical_list: D002118:Calcium; D004791:Enzyme Inhibitors; D008024:Ligands; D048068:PPAR-beta; D009195:Peroxidase; D013755:Tetradecanoylphorbol Acetate; D013844:Thiazoles; C479979:(4-(((2-(3-fluoro-4-(trifluoromethyl)phenyl)-4-methyl-1,3-thiazol-5-yl)methyl)sulfanyl)-2-methylphenoxy)acetic acid; D010636:Phenols; D013438:Sulfhydryl Compounds