Centre National de la Recherche Scientifique, Laboratory of Therapeutic Immunology and Chemistry, Unité Propre de Recherche 9021, Institut de Biologie Moléculaire et Cellulaire, University of Strasbourg, 67084 Strasbourg, France.
Proc Natl Acad Sci U S A. 2011 Mar 29;108(13):5342-7. doi: 10.1073/pnas.1013054108. Epub 2011 Mar 14.
Receptor activator of NF-κB (RANK), known for controlling bone mass, has been recognized for its role in epithelial cell activation of the mammary gland. Because bone and the epidermo-pilosebaceous unit of the skin share a lifelong renewal activity where similar molecular players operate, and because mammary glands and hair follicles are both skin appendages, we have addressed the function of RANK in the hair follicle and the epidermis. Here, we show that mice deficient in RANK ligand (RANKL) are unable to initiate a new growth phase of the hair cycle and display arrested epidermal homeostasis. However, transgenic mice overexpressing RANK in the hair follicle or administration of recombinant RANKL both activate the hair cycle and epidermal growth. RANK is expressed by the hair follicle germ and bulge stem cells and the epidermal basal cells, cell types implicated in the renewal of the epidermo-pilosebaceous unit. RANK signaling is dispensable for the formation of the stem cell compartment and the inductive hair follicle mesenchyme, and the hair cycle can be rescued by Rankl knockout skin transplantation onto nude mice. RANKL is actively transcribed by the hair follicle at initiation of its growth phase, providing a mechanism for stem cell RANK engagement and hair-cycle entry. Thus, RANK-RANKL regulates hair renewal and epidermal homeostasis and provides a link between these two activities.
核因子-κB 受体激活物（RANK），以控制骨量而闻名，其在乳腺上皮细胞激活中的作用已得到认可。由于骨骼和皮肤的表皮-毳毛-皮脂腺单位具有终身更新活性，并且乳腺和毛囊都是皮肤附属物，因此我们研究了 RANK 在毛囊和表皮中的功能。在这里，我们发现缺乏 RANK 配体（RANKL）的小鼠无法启动新的毛发生长周期，并且显示出表皮稳态的停滞。然而，在毛囊或表皮中过表达 RANK 的转基因小鼠或给予重组 RANKL 均可激活毛发生长周期和表皮生长。RANK 由毛囊生发中心和隆起干细胞以及表皮基底层细胞表达，这些细胞类型与表皮-毳毛-皮脂腺单位的更新有关。RANK 信号对于干细胞区室和诱导性毛囊间充质的形成是可有可无的，并且可以通过将 Rankl 敲除皮肤移植到裸鼠上来挽救毛发生长周期。在毛发生长周期开始时，毛囊会主动转录 RANKL，为干细胞 RANK 结合和毛发生长周期进入提供了一种机制。因此，RANK-RANKL 调节毛发更新和表皮稳态，并为这两种活动提供了联系。
