Center for Clinical and Experimental Photo-Dermatology, The Saarland University Hospital, 66421 Homburg, Germany and Department of Dermatology, The Saarland University Hospital, 66421 Homburg, Germany.
Photochem Photobiol Sci. 2017 Mar 16;16(3):433-444. doi: 10.1039/c6pp00280c.
During evolution, the ability of many organisms to synthesize vitamin D photochemically represented, and still represents, a major driving factor for the development of life on earth. In humans because not more than 10-20% of the requirement of vitamin D can be satisfied by the diet (under most living conditions in the US and Europe), the remaining 80-90% need to be photochemically synthesized in the skin through the action of solar or artificial ultraviolet-B (UV-B) radiation. The skin is a key organ of the human body's vitamin D endocrine system (VDES), representing both the site of vitamin D synthesis and a target tissue for biologically active vitamin D metabolites. Human keratinocytes contain the enzymatic machinery (CYP27B1) for the synthesis of the biologically most active natural vitamin D metabolite 1,25-dihydroxyvitamin D (1,25(OH)D), representing an autonomous vitamin D pathway. Cutaneous production of 1,25(OH)D may mediate intracrine, autocrine and paracrine effects on keratinocytes and on neighboring cells. Many skin cells (including keratinocytes, sebocytes, fibroblasts, melanocytes, macrophages and other skin immune cells) express the vitamin D receptor (VDR), an absolute pre-requisite for exerting genomic effects of 1,25(OH)D and analogs. The VDR is a member of the superfamily of trans-acting transcriptional regulatory factors, which also contains the steroid and thyroid hormone receptors as well as the retinoid-X receptors (RXR) and retinoic acid receptors (RAR). A large body of evidence, including cDNA microarray analyses of mRNAs, indicates that as many as 500-1000 genes may be controlled by VDR ligands that regulate a broad variety of cellular functions including growth, differentiation, and apoptosis. Clinical and laboratory investigations, including the observation that 1,25(OH)D is very effective in inducing the terminal differentiation and in inhibiting the proliferation of cultured human keratinocytes have resulted in the use of 1,25(OH)D and analogs for the treatment of psoriasis. Focussing on the UV-induced cutaneous synthesis of vitamin D, this review gives an update on the relevance of the VDES and of UV radiation for the management of psoriasis and other inflammatory skin diseases.
在进化过程中，许多生物体合成维生素 D 的能力在光化学上表现出来，并且仍然代表着地球上生命发展的主要驱动力。在人类中，由于饮食中只能满足维生素 D 需求的 10-20%（在美国和欧洲的大多数生活条件下），其余 80-90%需要通过皮肤在太阳或人工紫外线-B（UV-B）辐射的作用下光化学合成。皮肤是人体维生素 D 内分泌系统（VDES）的关键器官，既是维生素 D 合成的部位，也是生物活性维生素 D 代谢物的靶组织。人类角质形成细胞含有合成生物活性最强的天然维生素 D 代谢物 1,25-二羟基维生素 D（1,25(OH)D）的酶机制（CYP27B1），代表自主的维生素 D 途径。皮肤产生 1,25(OH)D 可能介导角质形成细胞和邻近细胞的细胞内、自分泌和旁分泌作用。许多皮肤细胞（包括角质形成细胞、皮脂细胞、成纤维细胞、黑素细胞、巨噬细胞和其他皮肤免疫细胞）表达维生素 D 受体（VDR），这是发挥 1,25(OH)D 和类似物基因组作用的绝对先决条件。VDR 是转录调节因子超家族的成员，其中还包括甾体和甲状腺激素受体以及视黄醇 X 受体（RXR）和维甲酸受体（RAR）。大量证据，包括 mRNA 的 cDNA 微阵列分析，表明多达 500-1000 个基因可能受 VDR 配体控制，这些配体调节包括生长、分化和凋亡在内的广泛细胞功能。临床和实验室研究，包括观察到 1,25(OH)D 非常有效地诱导培养的人角质形成细胞的终末分化和抑制增殖，导致 1,25(OH)D 和类似物用于治疗银屑病。本文聚焦于维生素 D 的皮肤光化学合成，综述了 VDES 和紫外线辐射对银屑病和其他炎症性皮肤病治疗的相关性。
