Nature Cell Biology ( IF 21.3 ) Pub Date : 2023-01-30 , DOI: 10.1038/s41556-022-01065-w Pieter Martino 1, 2 , Raghava Sunkara 1, 2 , Nicholas Heitman 1, 2, 3 , Martina Rangl 1, 2 , Alexia Brown 1, 2 , Nivedita Saxena 1, 2, 3 , Laura Grisanti 1, 2 , Donald Kohan 4 , Masashi Yanagisawa 5 , Michael Rendl 1, 2, 3, 6
Substantial follicle remodelling during the regression phase of the hair growth cycle is coordinated by the contraction of the dermal sheath smooth muscle, but how dermal-sheath-generated forces are regulated is unclear. Here, we identify spatiotemporally controlled endothelin signalling—a potent vasoconstriction-regulating pathway—as the key activating mechanism of dermal sheath contraction. Pharmacological blocking or genetic ablation of both endothelin receptors, ETA and ETB, impedes dermal sheath contraction and halts follicle regression. Epithelial progenitors at the club hair–epithelial strand bottleneck produce the endothelin ligand ET-1, which is required for follicle regression. ET signalling in dermal sheath cells and downstream contraction is dynamically regulated by cytoplasmic Ca2+ levels through cell membrane and sarcoplasmic reticulum calcium channels. Together, these findings illuminate an epithelial–mesenchymal interaction paradigm in which progenitors—destined to undergo programmed cell death—control the contraction of the surrounding sheath smooth muscle to orchestrate homeostatic tissue regression and reorganization for the next stem cell activation and regeneration cycle.
中文翻译:
祖源内皮素控制毛囊退化的真皮鞘收缩
在毛发生长周期的回归阶段,毛囊的大量重塑是通过真皮鞘平滑肌的收缩来协调的,但真皮鞘产生的力是如何调节的尚不清楚。在这里,我们将时空控制的内皮素信号传导(一种有效的血管收缩调节途径)确定为真皮鞘收缩的关键激活机制。内皮素受体 ETA 和 ETB 的药物阻断或基因消融会阻碍真皮鞘收缩并阻止毛囊退化。球状毛发-上皮链瓶颈处的上皮祖细胞产生内皮素配体 ET-1,这是卵泡退化所必需的。真皮鞘细胞中的 ET 信号传导和下游收缩受到细胞质 Ca 2+水平通过细胞膜和肌浆网钙通道的动态调节。总之,这些发现阐明了上皮-间质相互作用的范例,其中注定要经历程序性细胞死亡的祖细胞控制周围鞘平滑肌的收缩,以协调稳态组织的退化和重组,以进行下一个干细胞激活和再生周期。