Caveolin-1 expression in different types of psoriatic lesions: Analysis of 66 cases

Abstract

Background:Caveolin-1 is a key structural and functional protein. 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.Objectives:To examine the expression of caveolin-1 in skin biopsies from normal subjects, patients, and subjects with the three respective isoforms of psoriasis (psoriasis vulgaris, localized pustular psoriasis, and erythrodermic psoriasis). The expression level of caveolin-1 was compared among psoriasis vulgaris, localized pustular psoriasis, erythrodermic psoriasis, and normal subjects.Materials and Methods:Using immunohistochemical methods, caveolin-1 protein expression was assayed in four groups. An analysis was conducted on skin samples obtained from 22 normal subjects and 28 patients with psoriasis vulgaris, 22 patients with localized pustular psoriasis, and 16 patients with erythrodermic psoriasis. The statistical analysis of the scoring criteria reflecting the level of Caveolin-1 immunostaining between different groups was determined using the Mann–Whitney U-test.Results:In the normal skin, intense and consistent caveolin-1 staining was present in 22 cases. The Caveolin-1 protein was significantly reduced and showed very weak or absent staining within the tissues of psoriasis vulgaris, localized pustular psoriasis, and erythrodermic psoriasis (respective P < 0.001). Caveolin-1 protein expression in psoriasis vulgaris was higher than that in localized pustular psoriasis and erythrodermic psoriasis (respective P < 0.05). Caveolin-1 protein expression was no different in localized pustular psoriasis and erythrodermic psoriasis (P > 0.05).Conclusion:The finding of this study was consistent with a downregulation of Caveolin-1, which might serve as an etiological factor in the development of psoriasis vulgaris, localized pustular psoriasis, and erythrodermic psoriasis. Further mechanistic investigations are required to prove that Caveolin-1 protein has the potential and may be a novel target for therapy of psoriasis vulgaris, localized pustular psoriasis, and erythrodermic psoriasis.

Impact of NB‐UVB phototherapy on Caveolin‐1 expression in chronic plaque psoriasis

“…In the current work, the intensity of Cav‐1 immunohistochemical staining showed significant reduction in psoriatic plaques when compared to the apparently normal skin of psoriatic patients as well as normal control skin of healthy volunteers, which signifies its evident role in disease pathogenesis. These results agreed with those of several previous studies 7–10 that reported marked Cav‐1 downregulation in psoriatic lesions than normal healthy skin. Zhang et al, 7 suggested that reduction of Cav‐1 may encourage certain cellular and biochemical alterations triggering psoriasis, for example; (i) stimulation of mitotic divisions of basal keratinocytes with acceleration of epidermal turnover, leading to excessive epidermal hyperplasia, (ii) activation of anti‐apoptotic mechanisms, and/or (iii) inhibition of intracellular Ca 2 + mobilization, resulting in impairment of keratinocyte differentiation.…”

“…These results agreed with those of several previous studies 7–10 that reported marked Cav‐1 downregulation in psoriatic lesions than normal healthy skin. Zhang et al, 7 suggested that reduction of Cav‐1 may encourage certain cellular and biochemical alterations triggering psoriasis, for example; (i) stimulation of mitotic divisions of basal keratinocytes with acceleration of epidermal turnover, leading to excessive epidermal hyperplasia, (ii) activation of anti‐apoptotic mechanisms, and/or (iii) inhibition of intracellular Ca 2 + mobilization, resulting in impairment of keratinocyte differentiation. Yamaguchi et al, 9 proposed that Cav‐1 reduction in psoriatic lesions can augment keratinocyte hyperproliferation via stimulation of the JAK/STAT3 signalling pathway.…”

Rhododendrin inhibits toll-like receptor-7-mediated psoriasis-like skin inflammation in mice

“…Loss of caveolin-1 in epidermal keratinocytes has been shown to contribute to the development of psoriasis. 36 , 37 , 38 , 39 Therefore, we evaluated whether rhododendrin also regulates caveolin-1 expression. Surprisingly, caveolin-1 expression was found to be preserved with downregulation of TLR-7 upon treatment with rhododendrin compared with keratinocytes treated with IMQ alone, suggesting that rhododendrin exerts a critical therapeutic action in the maintenance of skin homeostasis during disease pathogenesis ( Figures 5a and b ).…”

“…It has been shown that the expression level of caveolin-1 is strikingly decreased and its spatial pattern of expression is altered in psoriatic skin. 36 , 37 , 38 , 39 Considerable work has been done to correlate caveolin-1 expression and the activity of receptor kinases with their respective downstream effects. 44 Activation of receptor tyrosine kinases and of the downstream p42/p44 MAP kinase pathway has been implicated in the keratinocyte hyperproliferation that is commonly associated with the pathogenesis of psoriasis.…”

Erythrodermic psoriasis: pathophysiology and current treatment perspectives

“…Additional histological features of EP include some features of classical psoriasis, including parakeratosis, acanthosis, spongiosis, Munro micro-abscesses, and occasional apoptotic keratinocytes. 13 , 15 , 16 However, due to exfoliation and loss of the epidermal stratum corneum in EP, Munro micro-abscesses and parakeratosis may not be prominent histologically. 13 Furthermore, in order to confirm a diagnosis of EP, clinicians must rule out other plausible causes of erythroderma such as atopic dermatitis, pityriasis rubra pilaris, drug eruptions, contact dermatitis, seborrheic dermatitis, immunobullous disorders, connective tissue disorders, and Sezary syndrome and other malignancies.…”