PPARβ/δ selectively induces differentiation and inhibits cell proliferation

Peroxisome proliferator-activated receptor ( PPAR) beta-null mice exhibit exacerbated epithelial cell proliferation and enhanced sensitivity to skin carcinogenesis, suggesting that ligand activation of PPAR beta will inhibit keratinocyte proliferation. By using of a highly specific ligand ( GW0742) and the PPAR beta-null mouse model, activation of PPARb 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 PPARb. These data suggest that ligand activation of PPARb 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.