The vitamin D3 receptor and retinoid X receptors in psoriatic skin: the receptor levels correlate with the receptor binding to DNA.
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.
Jensen
T
T
Department of Dermatology, Marselisborg Hospital, Aarhus, Denmark.
Sørensen
S
S
Sølvsten
H
H
Kragballe
K
K
D002352:Carrier Proteins / Q000032:analysis* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D011485:Protein Binding; D011565:Psoriasis / Q000378:metabolism*; D018167:Receptors, Calcitriol / Q000032:analysis* / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear; D012044:Regression Analysis; D015398:Signal Transduction; D012867:Skin / Q000378:metabolism*; D018709:Statistics, Nonparametric; D014809:Vitamin D-Binding Protein / Q000378:metabolism
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D018167:Receptors, Calcitriol; D018160:Receptors, Cytoplasmic and Nuclear; D014809:Vitamin D-Binding Protein