A melanocortin receptor 1 and 5 antagonist inhibits sebaceous gland differentiation and the production of sebum-specific lipids
A melanocortin receptor 1 and 5 antagonist inhibits sebaceous gland differentiation and the production of sebum-specific lipids
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DOI：
10.1016/j.jdermsci.2011.04.001
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发表时间：
2011-07-01
影响因子：
4.6
通讯作者：
Seiberg, Miri
中科院分区：
文献类型：
--
作者：
Eisinger, Magdalena;Li, Wen-Hwa;Seiberg, Miri
背景：黑素皮质素受体-5(MC5R)存在于人类皮脂腺中，仅在分化的皮脂细胞中表达。目的：研究MC5R在人皮脂腺中的生理功能。方法：用新型MC1R和MC5R拮抗剂(JNJ-10229570)处理原代培养的人皮脂细胞或移植到严重联合免疫缺陷小鼠的皮肤。结果：JNJ-10229570呈剂量依赖性抑制原代培养的人皮脂细胞皮脂脂的生成。用JNJ-10229570移植到SCID小鼠身上的人皮肤局部治疗后，皮脂特异性脂肪生成、皮脂腺大小和皮脂分化标记上皮膜抗原的表达显著减少。用已知的皮脂生成抑制剂氟他胺治疗，得到了类似的结果，验证了人类皮肤/SCID小鼠皮脂分泌实验系统。结论：我们的数据表明MC1R和MC5R的拮抗剂可能是有效的皮脂抑制药，可能有潜力治疗痤疮和其他皮脂腺病变。(C)2011年日本皮肤病研究学会。爱思唯尔爱尔兰有限公司出版。版权所有。
Background: The melanocortin receptor-5 (MC5R) is present in human sebaceous glands, where it is expressed in differentiated sebocytes only. The targeted disruption of MC5R in mice resulted in reduced sebaceous lipid production and a severe defect in water repulsion.Objective: To investigate the physiological function of MC5R in human sebaceous glands.Methods: A novel MC1R and MC5R antagonist (JNJ-10229570) was used to treat primary human sebaceous cells or human skins grafted onto severe combined immunodeficient (SCID) mice. Transcription profiling, lipid analyses, and histological and immunohistochemical staining were used to analyze the effect of MC5R inhibition on sebaceous gland differentiation and sebum production.Results: JNJ-10229570 dose dependently inhibited the production of sebaceous lipids in cultured primary human sebocytes. Topical treatment with JNJ-10229570 of human skins transplanted onto SCID mice resulted in a marked decrease in sebum-specific lipid production, sebaceous gland's size and the expression of the sebaceous differentiation marker epithelial-membrane antigen (EMA). Treatment with flutamide, a known inhibitor of sebum production, gave similar results, validating the human skin/SCID mouse experimental system for sebaceous secretion studies.Conclusion: Our data suggest that antagonists of MC1R and MC5R could be effective sebum suppressive agents and might have a potential for the treatment of acne and other sebaceous gland pathologies. (C) 2011 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.