Jensen T, Sørensen S, Sølvsten H, Kragballe K
Department of Dermatology, Marselisborg Hospital, Aarhus, Denmark.
Br J Dermatol. 1998 Feb;138(2):225-8. doi: 10.1046/j.1365-2133.1998.02065.x.
It is unknown whether vitamin D3 analogues improve psoriasis by overcoming an intrinsic abnormality of the vitamin D3 signalling pathway in psoriatic skin. The effects of vitamin D3 are mediated through the vitamin D3 receptor (VDR). The VDR heterodimerizes with another transcriptional regulator, preferentially the retinoid X receptor (RXR). In the present study the levels of VDR and RXR in involved and uninvolved psoriatic skin were determined by immunoblotting, and the binding of the VDR-RXR complex to a vitamin D3 response element (VDRE) consisting of two hexanucleotides spaced by three nucleotides (DR-3) by the electrophoretic mobility shift assay. The levels of VDR were similar in involved and uninvolved skin. RXR alpha, but neither RXR beta nor RXR gamma, was detectable. The RXR alpha levels were slightly lower in involved psoriatic skin than in uninvolved psoriatic skin, but this difference was statistically insignificant. The binding of VDR-RXR to the DR-3 VDRE was similar in uninvolved and involved psoriatic skin. Furthermore, there was a strong linear correlation between the levels of both VDR and RXR alpha and their binding to DNA. In conclusion, the initial part of the vitamin D3 signalling pathway involving receptor levels and receptor binding to DNA is normal in involved psoriatic skin.
目前尚不清楚维生素D3类似物是否通过克服银屑病皮肤中维生素D3信号通路的内在异常来改善银屑病。维生素D3的作用是通过维生素D3受体（VDR）介导的。VDR与另一种转录调节因子形成异二聚体，优先与视黄酸X受体（RXR）结合。在本研究中，通过免疫印迹法测定了银屑病受累皮肤和未受累皮肤中VDR和RXR的水平，并通过电泳迁移率变动分析测定了VDR-RXR复合物与由两个间隔三个核苷酸的六核苷酸组成的维生素D3反应元件（VDRE）（DR-3）的结合情况。受累皮肤和未受累皮肤中VDR的水平相似。可检测到RXRα，但未检测到RXRβ和RXRγ。银屑病受累皮肤中RXRα的水平略低于未受累皮肤，但这种差异无统计学意义。未受累和受累银屑病皮肤中VDR-RXR与DR-3 VDRE的结合相似。此外，VDR和RXRα的水平与其与DNA的结合之间存在很强的线性相关性。总之，在银屑病受累皮肤中，涉及受体水平和受体与DNA结合的维生素D3信号通路的起始部分是正常的。
