Department of Medicine, Stony Brook University, Stony Brook, NY, USA; Department of Medicine and Stony Brook Cancer Center, Stony Brook University, HSC T15-023, Stony Brook, NY 11794, USA; Graduate Program in Molecular and Cellular Biology, Stony Brook University, Stony Brook, NY, USA.
Department of Medicine, Stony Brook University, Stony Brook, NY, USA; Department of Medicine and Stony Brook Cancer Center, Stony Brook University, HSC T15-023, Stony Brook, NY 11794, USA.
Stem Cell Reports. 2017 Nov 14;9(5):1488-1500. doi: 10.1016/j.stemcr.2017.09.015. Epub 2017 Oct 19.
Ceramides and their metabolites are important for the homeostasis of the epidermis, but much remains unknown about the roles of specific pathways of ceramide metabolism in skin biology. With a mouse model deficient in the alkaline ceramidase (Acer1) gene, we demonstrate that ACER1 plays a key role in the homeostasis of the epidermis and its appendages by controlling the metabolism of ceramides. Loss of Acer1 elevated the levels of various ceramides and sphingoid bases in the skin and caused progressive hair loss in mice. Mechanistic studies revealed that loss of Acer1 widened follicular infundibulum and caused progressive loss of hair follicle stem cells (HFSCs) due to reduced survival and stemness. These results suggest that ACER1 plays a key role in maintaining the homeostasis of HFSCs, and thereby the hair follicle structure and function, by regulating the metabolism of ceramides in the epidermis.
神经酰胺及其代谢产物对于表皮的内稳态非常重要，但神经酰胺代谢的特定途径在皮肤生物学中的作用仍知之甚少。通过缺乏碱性神经酰胺酶 (Acer1) 基因的小鼠模型，我们证明 ACER1 通过控制神经酰胺的代谢，在表皮及其附属物的内稳态中发挥关键作用。Acer1 的缺失会升高皮肤中各种神经酰胺和鞘氨醇碱基的水平，并导致小鼠逐渐脱发。机制研究表明，Acer1 的缺失会扩大毛囊漏斗部，并由于生存能力和干性降低而导致毛囊干细胞 (HFSCs) 逐渐丢失。这些结果表明，ACER1 通过调节表皮中神经酰胺的代谢，在维持 HFSCs 的内稳态以及毛囊结构和功能方面发挥关键作用。
