The 1,25-dihydroxyvitamin D3-independent actions of the vitamin D receptor in skin.
The 1,25-dihydroxyvitamin D3-independent actions of the vitamin D receptor in skin.
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DOI：
10.1016/j.jsbmb.2010.03.072
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发表时间：
2010-07
影响因子：
4.1
通讯作者：
MacDonald, Paul N.
中科院分区：
文献类型：
--
作者：
Dowd, Diane R.;MacDonald, Paul N.
维生素D内分泌系统在皮肤和毛囊循环中起着重要但知之甚少的作用。罕见的人类遗传疾病和基因敲除小鼠模型突出了皮肤中维生素D内分泌系统的重要作用和潜在的新机制。维生素D受体敲除小鼠表达毛囊周期缺陷和过度增殖表型，导致皮肤结构紊乱、表皮增厚和脱发。相反，配体敲除小鼠（即，编码25-羟维生素-D3 1α-羟化酶的CYP 27 B1基因被破坏的小鼠）具有正常的毛囊功能和相对适度的皮肤表型。这些不同的模型表明，VDR可能独立于1，25-二羟维生素D3（1，25（OH）2D 3）在调节毛囊周期和皮肤生物学中发挥作用。最近的研究强调了这一概念，并为这一假设提供了关键支持。虽然VDR敲除小鼠对化学诱导的皮肤肿瘤发生高度敏感，但CYP 27 B1敲除小鼠具有抗性。这些研究揭示了皮肤中的第二个整体生理过程，该过程可能由VDR以1，25（OH）2D 3-独立的方式调节，即对致癌诱变剂的遗传保护。最近发表的支持这一机制的关键细胞和分子数据显示，VDR介导的角质形成细胞选择性反式激活活性不依赖于1，25（OH）2D 3配体。因此，证据正在建立，以支持一种潜在的新的，1，25（OH）2D 3-独立的机制，通过该机制，VDR在角质形成细胞中发挥作用，并可能在毛囊中的干细胞群中调节皮肤中的基因保护和其他关键发育过程。
The vitamin D endocrine system plays important but poorly understood roles in the skin and in hair follicle cycling. Rare, human genetic disorders and knockout mouse models highlight essential roles and potentially novel mechanisms of the vitamin D endocrine system in the skin. Vitamin D receptor knockout mice express a hair follicle cycling defect and a hyperproliferative phenotype resulting in disordered skin structure, epidermal thickening, and alopecia. In contrast, ligand knockout mice (i.e., mice with a disrupted CYP27B1 gene that encodes the 25-hydroxyvitamin-D3 1α-hydroxylase) have normal hair follicle function and a comparatively modest skin phenotype. These disparate models indicate that VDR may function independently of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in regulating hair follicle cycling and skin biology. Recent studies highlight this concept and provide key support for this hypothesis. While VDR knockout mice are highly susceptible to chemically-induced skin tumorigenesis, CYP27B1 knockouts are resistant. These studies reveal a second global physiological process in the skin that may be regulated by VDR in a 1,25(OH)2D3-independent fashion, namely, genoprotection against carcinogenic mutagens. Key cellular and molecular data supporting this mechanism were published recently showing a keratinocyte-selective transactivation activity mediated by VDR that is independent of the 1,25(OH)2D3 ligand. Thus, evidence is building to support a potentially novel, 1,25(OH)2D3-independent mechanism through which VDR functions in keratinocytes and perhaps within stem cell populations in the follicle to regulate genoprotection and other key developmental processes in the skin.
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影响因子：
56.9
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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