Skin Research Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore.
Centre for Dermatology Research, University of Manchester, and NIHR Manchester Biomedical Research Centre, Manchester, U.K.
Br J Dermatol. 2019 Oct;181(4):677-690. doi: 10.1111/bjd.17981. Epub 2019 May 6.
Sebaceous glands (SGs) are appendages of mammalian skin that produce a mixture of lipids known as sebum. Acne vulgaris is an exceptionally common skin condition, characterized by elevated sebum production, altered sebum composition, and the formation of infundibular cysts, called comedones. Comedo-associated SGs are atrophic, suggesting that comedo formation involves abnormal differentiation of progenitor cells that generate the SG and infundibulum: the 'comedo switch'. Understanding the biological processes that govern SG homeostasis promises to highlight potential aetiological mechanisms underlying acne and other SG-associated skin disorders.
In this review, we discuss the clinical data, genetic mouse models and in vitro research that have highlighted major hormones, paracrine factors, transcription factors and signalling pathways that control SG homeostasis. These include, but are not limited to androgens, progestogens and oestrogens; retinoids; receptor tyrosine kinases such as ErbB family receptors, fibroblast growth factor receptor 2 and insulin/insulin-like growth factor 1 receptors; peroxisome proliferator-activated receptor γ; aryl hydrocarbon receptor; and the Wnt signalling pathway. Where possible, the cellular and molecular mechanisms by which these regulatory factors control SG biology are indicated, along with considerations as to how they might contribute to acne pathogenesis.
Future research should seek to establish the relative importance, and causative relationships, of altered sebum production, sebum composition, inflammation and abnormal differentiation of sebaceous progenitors to the process of comedo formation in acne. Such an understanding will allow for therapeutic targeting of regulatory factors that control SG homeostasis, with the aim of treating acne.
皮脂腺（SGs）是哺乳动物皮肤的附属物，可产生称为皮脂的脂质混合物。寻常痤疮是一种极其常见的皮肤疾病，其特征是皮脂产生增加、皮脂成分改变以及形成称为粉刺的囊状凹陷。与粉刺相关的 SG 是萎缩的，这表明粉刺的形成涉及产生 SG 和漏斗部的祖细胞的异常分化：即“粉刺开关”。了解控制 SG 稳态的生物学过程有望突出痤疮和其他与 SG 相关的皮肤疾病的潜在病因机制。
在这篇综述中，我们讨论了突出控制 SG 稳态的主要激素、旁分泌因子、转录因子和信号通路的临床数据、遗传小鼠模型和体外研究。这些包括但不限于雄激素、孕激素和雌激素；类视黄醇；受体酪氨酸激酶，如表皮生长因子受体家族、成纤维细胞生长因子受体 2 和胰岛素/胰岛素样生长因子 1 受体；过氧化物酶体增殖物激活受体 γ；芳烃受体；以及 Wnt 信号通路。在可能的情况下，指出了这些调节因子控制 SG 生物学的细胞和分子机制，并考虑了它们如何促成痤疮发病机制。
未来的研究应该致力于确定皮脂产生、皮脂成分、炎症和皮脂腺祖细胞异常分化改变对痤疮中粉刺形成过程的相对重要性和因果关系。这种理解将允许针对调节 SG 稳态的调节因子进行治疗靶向，以治疗痤疮。
