Epidermis is known to have de novo synthetic pathway of cholesterol via HMG-CoA reductase. The influence of inhibition cholesterol de novo synthetic path on epidermal homeostasis is not fully understood. To analyze the influence of HMG-CoA reductase inhibitor (pitavastatin) on epidermal homeostasis, gene array analysis was employed. RNA from pitavastatin-treated cultured keratinocytes was harvested and gene expression profiles was made by the results of gene array analysis. The expressed genes with differential of over 2 times compared to that of no-treated keratinocyte were extracted, and confirmed by real time PCR. Furthermore, both immunohistochemistry and in situ hybridization were employed for histological analysis. We focused on the decreased expression of TNFAIP3, and Claudin-7 by treatment with pitavastatin, which were confirmed in real-time PCR. In histological analysis, claudin-7 is strongly expressed in sweat glands, but not in epidermis of normal skin. Regarding the skin diseases, immunohistochemical analysis revealed the highly expressed claudin-7 in the stratum granulosum of the psoriatic skin lesions, while the expression of claudin-7 in that of non-lesion of psoriasis was scanty. These results suggested that claudin-7 was possibly regulated by HMG-CoA reductase and thereby showed strong expression in the epidermal stratum granulosum of psoriasis. Claudin-7 might be involved in the pathogenesis of psoriasis.

Claudin-7 in keratinocyte is downregulated by inhibition of HMG-CoA reductase, and is highly expressed in the stratum granulosum of psoriatic epidermis