Downregulation and altered spatial pattern of caveolin-1 in chronic plaque psoriasis

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Abstract
Summary 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. Objectives 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.