Peroxisome proliferator-activated receptors increase human sebum production
Peroxisome proliferator-activated receptors increase human sebum production
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DOI：
10.1038/sj.jid.5700336
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发表时间：
2006-09-01
影响因子：
6.5
通讯作者：
Thiboutot, Diane M.
中科院分区：
文献类型：
--
作者：
Trivedi, Nishit R.;Cong, Zhaoyuan;Thiboutot, Diane M.
皮脂产生是痤疮病理生理学的关键，痤疮是一种非常常见的疾病，严重时可能需要用异维甲酸（一种已知的致畸剂）治疗。除了异维甲酸和激素治疗，没有药物可用于减少皮脂。增加我们对皮脂产生调节的理解是确定替代治疗靶点的里程碑。对皮脂细胞和人类皮脂腺的研究表明，过氧化物酶体增殖物激活受体（PPARs）的激动剂可改变皮脂脂质的产生。本研究的目的是验证PPARs在人皮肤和SEB-1皮脂细胞中的表达和活性，并评估PPAR配体对患者皮脂产生的影响。为了研究每种受体亚型对皮脂产生的贡献，在用PPAR配体和异维甲酸处理的SEB-1皮脂细胞中进行脂肪生成测定。异维甲酸显著降低脂肪生成，而PPAR α激动剂GW 7647、PPAR δ激动剂-GW 0742、PPAR α/δ激动剂-GW 2433、PPAR γ激动剂罗格列酮和泛激动剂-GW 4148增加脂肪生成。与年龄、疾病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的皮脂生成显著增加（分别为37%和77%）。这些数据表明，PPARs在调节皮脂产生中起作用，并且选择性调节其活性可能代表治疗痤疮的新治疗策略。
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 PPAR alpha agonist GW7647, PPAR delta agonist-GW0742, PPAR alpha/delta agonist-GW2433, PPAR gamma 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.