The vitamin D receptor, the skin and stem cells.
The vitamin D receptor, the skin and stem cells.
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维生素 D 受体、皮肤和干细胞。
DOI：
10.1016/j.jsbmb.2010.01.015
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Demay,MarieB
中科院分区：
文献类型：
--
作者：
Luderer,HilaryF;Demay,MarieB
维生素D的活性代谢物1，25-二羟基维生素D已被证明对角质形成细胞具有促分化和抗增殖作用，其通过与其核受体的相互作用介导。维生素D受体的其他皮肤作用已经通过具有非功能性维生素D受体的人类和小鼠的皮肤表型而被揭示。虽然缺乏功能性维生素D受体的小鼠发育出正常的第一层毛发，但它们表现出毛囊周期性再生受损，导致脱发的发展。正常的毛发循环涉及毛乳头和表皮角质形成细胞之间的相互作用。在小鼠中进行的维生素D受体靶向消融研究表明，毛发周期的异常是由于毛囊角质形成细胞成分的缺陷。此外，突变型维生素D受体转基因在维生素D受体敲除小鼠的角质形成细胞中的表达表明，维持毛囊稳态的受体的作用是不依赖于配体的。功能性维生素D受体的缺乏导致角质形成细胞干细胞在体内和体外的功能受损。这表现为毛囊的周期性再生受损、隆突角质形成细胞干细胞随着衰老而减少以及这些细胞的谱系进展异常，导致它们优先分化为皮脂腺细胞。
The active metabolite of vitamin D, 1,25-dihydroxyvitamin D, has been shown to have pro-differentiation and antiproliferative effects on keratinocytes that are mediated by interactions with its nuclear receptor. Other cutaneous actions of the vitamin D receptor have been brought to light by the cutaneous phenotype of humans and mice with non-functional vitamin D receptors. Although mice lacking functional vitamin D receptors develop a normal first coat of hair, they exhibit impaired cyclic regeneration of hair follicles that leads to the development of alopecia. Normal hair cycling involves reciprocal interactions between the dermal papilla and the epidermal keratinocyte. Studies in mice with targeted ablation of the vitamin D receptor demonstrate that the abnormality in the hair cycle is due to a defect in the keratinocyte component of the hair follicle. Furthermore, expression of mutant vitamin D receptor transgenes in the keratinocytes of vitamin D receptor knockout mice demonstrates that the effects of the receptor that maintain hair follicle homeostasis are ligand-independent. Absence of a functional vitamin D receptor leads to impaired function of keratinocyte stem cells, both in vivo and in vitro. This is manifested by impaired cyclic regeneration of the hair follicle, a decrease in bulge keratinocyte stem cells with ageing and an abnormality in lineage progression of these cells, leading to their preferential differentiation into sebocytes.