Defective cyclic guanosine monophosphate-gated calcium channels and the pathogenesis of psoriasis.
A positive association between intake of calcium channel blockers and psoriasis has been observed recently. Intake of blockers of voltage-gated calcium ion channels is associated with outbreaks of psoriasis after a latent period in patients with and without a previous family history of psoriasis. This suggests that interfering with calcium influx may trigger psoriasis. Calcium influx also occurs via cyclic guanosine monophosphate-gated channels; human keratinocytes contain functional and non-functional (splice variants) versions of these channels. We show here that keratinocytes and skin from psoriatic individuals express higher levels of mRNA encoding a non-functional cyclic guanosine monophosphate-gated calcium channel and that high expression of the splice variant by transfection of cells in culture leads to loss of protein expression for the functional cyclic guanosine monophosphate-gated Ca2+ channels.
McKenzie
Roddie C
RC
Epidermal Inflammation and Protection Group, Department of Dermatology, University of Edinburgh, Edinburgh, Scotland, UK. Roddie.McKenzie@ed.ac.uk
Oda
Yuko
Y
Szepietowski
Jacek C
JC
Behne
Martin J
MJ
Mauro
Theodora
T
D000328:Adult; D000368:Aged; D001707:Biopsy, Needle; D015220:Calcium Channels / Q000378:metabolism*; D020013:Calcium Signaling; D016022:Case-Control Studies; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D015640:Ion Channel Gating; D015603:Keratinocytes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011336:Probability; D011565:Psoriasis / Q000235:genetics / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric
D015220:Calcium Channels; D005819:Genetic Markers; D012333:RNA, Messenger; D006152:Cyclic GMP