PPAR-γ 信号通路作为人类毛囊生理学和病理学的关键介质。
PPAR-γ signalling as a key mediator of human hair follicle physiology and pathology.
机构信息
Department of Dermatology, Hadassah Medical Center, The Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
Monasterium Laboratory, Skin and Hair Research Solutions GmbH, Muenster, Germany.
出版信息
Exp Dermatol. 2020 Mar;29(3):312-321. doi: 10.1111/exd.14062. Epub 2019 Dec 17.
Peroxisome proliferator-activated receptors (PPARs) are abundantly expressed in human skin, with PPAR-γ being the most intensively investigated isoform. In various ex vivo and in vivo models, PPAR-γ-mediated signalling has recently surfaced as an essential element of hair follicle (HF) development, growth and stem cell biology. Moreover, the availability of novel, topically applicable PPAR-γ modulators with a favourable toxicological profile has extended the range of potential applications in clinical dermatology. In this review, we synthesize where this field currently stands and sketch promising future research avenues, focussing on the role of PPAR-γ-mediated signalling in the biology and pathology of human scalp HFs, with special emphasis on scarring alopecias such as lichen planopilaris and frontal fibrosing alopecia as model human epithelial stem cell diseases. In particular, we discuss whether and how pharmacological modulation of PPAR-γ signalling may be employed for the management of hair growth disorders, for example, in scarring alopecia (by reducing HF inflammation as well as by promoting the survival and suppressing pathological epithelial-mesenchymal transition of keratin 15 + epithelial stem cells in the bulge) and in hirsutism/hypertrichosis (by promoting catagen development). Moreover, we explore the potential role of PPAR-γ in androgenetic alopecia, HF energy metabolism and HF ageing, and consider clinical perspectives that emanate from the limited data available on this so far. As this field of translational human hair research is still in its infancy, many open questions exist, for which we briefly delineate selected experimental approaches that promise to generate instructive answers in the near future.
过氧化物酶体增殖物激活受体 (PPARs) 在人类皮肤中大量表达,其中 PPAR-γ 是研究最为深入的亚型。在各种离体和体内模型中,PPAR-γ 介导的信号转导最近被发现是毛囊 (HF) 发育、生长和干细胞生物学的重要组成部分。此外,新型、局部应用的具有良好毒理学特征的 PPAR-γ 调节剂的出现,扩展了其在临床皮肤科潜在应用的范围。在这篇综述中,我们综合了该领域的现状,并勾勒出了有前途的未来研究方向,重点关注 PPAR-γ 介导的信号转导在人类头皮 HF 生物学和病理学中的作用,特别强调瘢痕性脱发,如扁平苔藓性瘢痕和额部纤维性脱发,作为人类上皮干细胞疾病的模型。具体而言,我们讨论了是否以及如何通过药理学调节 PPAR-γ 信号转导来治疗毛发生长障碍,例如在瘢痕性脱发中(通过减少 HF 炎症以及通过促进毛囊隆突中角蛋白 15+上皮干细胞的存活和抑制病理性上皮-间充质转化)和在多毛症/多毛症中(通过促进退行期的发展)。此外,我们探讨了 PPAR-γ 在雄激素性脱发、HF 能量代谢和 HF 老化中的潜在作用,并考虑了从目前有限的数据中得出的临床观点。由于这一转化性人类毛发研究领域仍处于起步阶段,存在许多悬而未决的问题,我们简要描述了一些有希望在不久的将来产生有指导意义答案的实验方法。