Downregulation and altered spatial pattern of caveolin-1 in chronic plaque psoriasis.
BACKGROUND
Caveolin-1 is a key structural and functional protein for plasmalemmal invaginations termed caveolae. Caveolin-1 is known to modulate multiple signal-transducing pathways involved in cell differentiation and proliferation. Psoriasis is viewed as a multifactorial pathology characterized by keratinocyte hyperproliferation and abnormal cell maturation. We hypothesized that loss of caveolin-1 within epidermal keratinocytes may contribute to the development and/or progression of the psoriatic phenotype.


OBJECTIVE
To examine the expression and spatial distribution of caveolin-1 in skin biopsies from normal subjects and in patients with psoriasis.


METHODS
Using immunohistochemical methods caveolin-1 protein expression was assayed in two independent patient groups. Firstly, a retrospective analysis was conducted on archival skin samples obtained from nine normal subjects and from involved tissue of 12 patients with psoriasis. Following this, a prospectively designed study was conducted in 10 further patients with active psoriasis and involving caveolin-1 staining of biopsy tissue from the uninvolved, advancing edge and lesional skin tissue from within the same subject.


RESULTS
In normal skin or uninvolved skin from psoriasis patients intense caveolin-1 staining was present throughout full-thickness epidermis. In 20 of the 22 patient cases (combined retrospective and prospective samples) caveolin-1 protein was significantly reduced and consistently showed very weak or absent staining within the hyperproliferative basal cell layers of the psoriatic plaque (P < 0.002 for retrospective archival study and P < 0.01 for prospectively designed study). Comparisons between caveolin-1 staining in uninvolved tissue and at the advancing edge of a migrating plaque were more equivocal (P > 0.05).


CONCLUSIONS
The findings of this study are consistent with a downregulation of caveolin-1 that may serve as an aetiological factor in the development and/or progression of psoriasis. Further mechanistic investigations are required with the potential that caveolin-1 protein may be a novel target for therapy of psoriasis.
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051242:Caveolin 1; D022461:Caveolins / Q000378:metabolism*; D002908:Chronic Disease; D015536:Down-Regulation; D004817:Epidermis / Q000378:metabolism; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011565:Psoriasis / Q000378:metabolism*; D012189:Retrospective Studies
C495540:CAV1 protein, human; D051242:Caveolin 1; D022461:Caveolins