In:
Experimental Dermatology, Wiley, Vol. 23, No. 7 ( 2014-07), p. 524-526
Abstract:
Netherton syndrome ( NS ; OMIM 256500) is a genetic skin disease resulting from defects in the serine protease inhibitor K azal‐type 5 ( SPINK 5) gene, which encodes the protease inhibitor lympho‐epithelial K azal type inhibitor ( LEKTI ). We established a SPINK 5 knockdown skin model by transfecting SPINK 5 small interfering RNA (si RNA ) 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 and loss of corneodesmosomes. As enhanced serine protease activity has been implicated in the disease pathogenesis, we investigated the impact of the kallikreins KLK 5 [stratum corneum trypsin‐like enzyme ( SCTE )] and KLK 7 [stratum corneum chymotrypsin‐like enzyme ( SCCE )] on the SPINK 5 knockdown phenotype by generating double knockdowns in the organotypic model. Knockdown of KLK 5 or KLK 7 partially ameliorated the epidermal architecture: increased epidermal thickness and expression of desmocollin 1 ( DSC 1), desmoglein 1 ( DSG 1) and (pro)filaggrin. Thus, inhibition of serine proteases KLK 5 and KLK 7 could be therapeutically beneficial in NS .
Type of Medium:
Online Resource
ISSN:
0906-6705
,
1600-0625
DOI:
10.1111/exd.2014.23.issue-7
Language:
English
Publisher:
Wiley
Publication Date:
2014
detail.hit.zdb_id:
2026228-0
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