Trivedi Nishit R, Cong Zhaoyuan, Nelson Amanda M, Albert Adam J, Rosamilia Lorraine L, Sivarajah Surendra, Gilliland Kathryn L, Liu Wenlei, Mauger David T, Gabbay Robert A, Thiboutot Diane M
The Jake Gittlen Cancer Research Institute, Hershey, Pennsylvania 17033, USA.
J Invest Dermatol. 2006 Sep;126(9):2002-9. doi: 10.1038/sj.jid.5700336. Epub 2006 May 4.
Sebum production is key in the pathophysiology of acne, an extremely common condition, which when severe, may require treatment with isotretinoin, a known teratogen. Apart from isotretinoin and hormonal therapy, no agents are available to reduce sebum. Increasing our understanding of the regulation of sebum production is a milestone in identifying alternative therapeutic targets. Studies in sebocytes and human sebaceous glands indicate that agonists of peroxisome proliferator-activated receptors (PPARs) alter sebaceous lipid production. The goal of this study is to verify the expression and activity of PPARs in human skin and SEB-1 sebocytes and to assess the effects of PPAR ligands on sebum production in patients. To investigate the contribution of each receptor subtype to sebum production, lipogenesis assays were performed in SEB-1 sebocytes that were treated with PPAR ligands and isotretinoin. Isotretinoin significantly decreased lipogenesis, while the PPARalpha agonist-GW7647, PPARdelta agonist-GW0742, PPARalpha/delta agonist-GW2433, PPARgamma agonist rosiglitazone, and the pan-agonist-GW4148, increased lipogenesis. Patients treated with thiazolidinediones or fibrates had significant increases in sebum production (37 and 77%, respectively) when compared to age-, disease-, and sex-matched controls. These data indicate that PPARs play a role in regulating sebum production and that selective modulation of their activity may represent a novel therapeutic strategy for the treatment of acne.
皮脂分泌是痤疮发病机制中的关键因素，痤疮是一种极为常见的病症，严重时可能需要使用异维A酸进行治疗，而异维A酸是一种已知的致畸剂。除了异维A酸和激素疗法外，目前尚无其他药物可用于减少皮脂分泌。加深我们对皮脂分泌调节机制的理解是确定替代治疗靶点的一个里程碑。对皮脂腺细胞和人皮脂腺的研究表明，过氧化物酶体增殖物激活受体（PPARs）的激动剂可改变皮脂腺脂质生成。本研究的目的是验证PPARs在人皮肤和SEB - 1皮脂腺细胞中的表达和活性，并评估PPAR配体对患者皮脂分泌的影响。为了研究每种受体亚型对皮脂分泌的作用，在经PPAR配体和异维A酸处理的SEB - 1皮脂腺细胞中进行了脂肪生成测定。异维A酸显著降低了脂肪生成，而PPARα激动剂 - GW7647、PPARδ激动剂 - GW0742、PPARα/δ激动剂 - GW2433、PPARγ激动剂罗格列酮以及泛激动剂 - GW4148则增加了脂肪生成。与年龄、病情和性别匹配的对照组相比，接受噻唑烷二酮类或贝特类药物治疗的患者皮脂分泌显著增加（分别为37%和77%）。这些数据表明，PPARs在调节皮脂分泌中发挥作用，对其活性进行选择性调节可能代表一种治疗痤疮的新型策略。
