Kim D J, Bility M T, Billin A N, Willson T M, Gonzalez F J, Peters J M
Department of Veterinary Science and The Center for Molecular Toxicology and Carcinogenesis, The Pennsylvania State University, University Park, PA 16802, USA.
Cell Death Differ. 2006 Jan;13(1):53-60. doi: 10.1038/sj.cdd.4401713.
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.
过氧化物酶体增殖物激活受体（PPAR）β基因敲除小鼠表现出上皮细胞增殖加剧以及对皮肤癌发生的敏感性增强，这表明PPARβ的配体激活将抑制角质形成细胞增殖。通过使用高度特异性配体（GW0742）和PPARβ基因敲除小鼠模型，发现PPARβ的激活可选择性诱导角质形成细胞终末分化并抑制角质形成细胞增殖。此外，发现GW0742具有抗炎作用，这是由于其对髓过氧化物酶活性的抑制，与PPARβ无关。这些数据表明，PPARβ的配体激活可能是一种选择性诱导分化并抑制细胞增殖的新方法，从而代表了治疗因细胞增殖改变导致的皮肤疾病（如银屑病和癌症）的新分子靶点。
