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SPINK5 knockdown in organotypic human skin culture as a model system for Netherton syndrome: effect of genetic inhibition of serine proteases

Wang, Shirley and Olt, Sabine and Schoefmann, Nicole and Stuetz, Anton and Winiski, Anthony and Wolff-Winiski, Barbara (2014) SPINK5 knockdown in organotypic human skin culture as a model system for Netherton syndrome: effect of genetic inhibition of serine proteases. Experimental Dermatology, 23 (7). pp. 524-526.

Abstract

Netherton Syndrome (NS) is a genetic skin disease resulting from defects in the SPINK5 gene, which encodes the protease inhibitor lympho-epithelial Kazal type inhibitor 1 (LEKTI). We established a SPINK5 knockdown skin model by transfecting SPINK5 small interfering RNA (siRNA) into normal human epidermal keratinocytes, which were used together with fibroblast-populated collagen gels to generate organotypic skin cultures. This model recapitulates some of the NS skin morphology: thicker, parakeratotic stratum corneum frequently detached from the underlying epidermis. Since enhanced serine protease activity has been implicated in the disease pathogenesis, we investigated the impact of the kallikreins KLK5 and KLK7 on the SPINK5 knockdown phenotype by generating double knockdowns in the organotypic model. Knockdown of KLK5 or KLK7 partially corrected the epidermal architecture: increased epidermal thickness and recovery of desmocollin1 (DSC1), Desmoglein 1 (DSG1) and (pro)filaggrin expression. Thus inhibition of serine proteases KLK5 and KLK7 could be therapeutically beneficial in NS.

Item Type: Article
Date Deposited: 13 Oct 2015 13:13
Last Modified: 13 Oct 2015 13:13
URI: https://oak.novartis.com/id/eprint/21015

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