Induction of vitamin D receptor mRNA expression in psoriatic plaques correlates with clinical response to 1,25-dihydroxyvitamin D3.
Psoriasis is a skin disorder characterized by hyperproliferation of epidermal keratinocytes. 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25(OH)2D3) and its analogs have been shown to inhibit keratinocyte proliferation in vitro and to be therapeutically effective for the treatment of psoriasis. Some patients with psoriasis, however, do not have a favorable response to 1 alpha,25 (OH)2D3 therapy. To evaluate the differential responsiveness to 1 alpha (OH)2D3 treatment, we examined the expression of vitamin D receptor mRNA in psoriatic lesions by reverse transcription-polymerase chain reaction using glyceraldehyde-3-phosphate dehydrogenase as an internal control. In this double-blind clinical trial, we recruited 18 patients who received topical treatment of 1 alpha,25(OH)2D3 (15 microgram/g Vaseline) or placebo on separated psoriatic lesions for 8 weeks. In patients who showed >90% clinical improvements of their psoriatic lesions with 1 alpha,25(OH)2D3 (n=9), an increase of 130+/-37% in vitamin D receptor mRNA level was observed in 1 alpha,25(OH)2D3-treated lesions when compared with the corresponding placebo controls. There was no increase in vitamin D receptor mRNA level in the lesions treated with this drug in patients who did not respond to the treatment. These data suggest that the antiproliferative activity of 1 alpha,25(OH)2D3 is closely associated with the expression of its cognate receptor.
Chen
M L
ML
Department of Medicine, Boston University Medical Center, Massachusetts, USA.
Perez
A
A
Sanan
D K
DK
Heinrich
G
G
Chen
T C
TC
Holick
M F
MF
D001483:Base Sequence; D002117:Calcitriol / Q000627:therapeutic use*; D004311:Double-Blind Method; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011565:Psoriasis / Q000188:drug therapy / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis*; D018167:Receptors, Calcitriol / Q000235:genetics*
D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D002117:Calcitriol