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Targeted silencing of DEFB 4 in a bioengineered skin‐humanized mouse model for psoriasis: development of si RNA SEC osome‐based novel therapies
Author(s) -
Bracke Stefanie,
Carretero Marta,
GuerreroAspizua Sara,
Desmet Eline,
Illera Nuria,
Navarro Manuel,
Lambert Jo,
Del Rio Marcela
Publication year - 2014
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.12321
Subject(s) - psoriasis , humanized mouse , medicine , stratum corneum , human skin , gene silencing , filaggrin , cancer research , immunology , pathology , biology , atopic dermatitis , immune system , gene , biochemistry , genetics
Psoriasis is a complex inflammatory skin disease that presents a wide variety of clinical manifestations. Human β defensin‐2 ( hBD ‐2) is highly up‐regulated in psoriatic lesions and has been defined as a biomarker for disease activity. We explored the potential benefits of targeting hBD ‐2 by topical application of DEFB4‐siRNA‐containing SECosomes in a bioengineered skin‐humanized mouse model for psoriasis. A significant improvement in the psoriatic phenotype was observed by histological examination, with a normalization of the skin architecture and a reduction in the number and size of blood vessels in the dermal compartment. Treatment leads to the recovery of transglutaminase activity, filaggrin expression and stratum corneum appearance to the levels similar to those found in normal regenerated human skin. The availability of a reliable skin‐humanized mouse model for psoriasis in conjunction with the use of the SECosome technology may provide a valuable preclinical tool for identifying potential therapeutic targets for this disease.