Targeted silencing of DEFB4 in a bioengineered skin-humanized mouse model for psoriasis: development of siRNA SECosome-based novel therapies

被引：51

作者：

Bracke, Stefanie ^{[1
]}

Carretero, Marta ^{[2
,3
]}

Guerrero-Aspizua, Sara ^{[3
,4
]}

Desmet, Eline ^{[1
]}

Illera, Nuria ^{[3
,5
]}

Navarro, Manuel ^{[6
]}

Lambert, Jo ^{[1
]}

Del Rio, Marcela ^{[3
,4
]}

机构：

[1] Ghent Univ Hosp, Dept Dermatol, Ghent, Belgium

[2] Ctr Invest Energet Medioambientales & Tecnol CIEM, Cutaneous Dis Modeling Unit, Epithelial Biomed Div, Basic Res Dept, Madrid, Spain

[3] ISCIII, Ctr Biomed Res Rare Dis CIBERER, Valencia, Spain

[4] Carlos III Univ UC3M, Dept Bioengn, Madrid 28911, Spain

[5] Ctr Invest Energet Medioambientales & Tecnol CIEM, Regenerat Med Unit, Basic Res Dept, Madrid, Spain

[6] Ctr Invest Energet Medioambientales & Tecnol CIEM, Mol Oncol Unit, Basic Res Dept, Madrid, Spain

来源：

EXPERIMENTAL DERMATOLOGY | 2014年 / 23卷 / 03期

关键词：

hBD-2; psoriasis; SECosomes; siRNA; skin-humanized mouse; INDUCED OXIDATIVE STRESS; NF-KAPPA-B; GENE-EXPRESSION; HUMAN KERATINOCYTES; IN-VITRO; ASTAXANTHIN; INFLAMMATION; APOPTOSIS; CELLS; PHOSPHORYLATION;

D O I：

10.1111/exd.12321

中图分类号：

R75 [皮肤病学与性病学];

学科分类号：

100227 [皮肤病学];

摘要：

Psoriasis is a complex inflammatory skin disease that presents a wide variety of clinical manifestations. Human beta 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.

引用

页码：199 / 201

页数：3

共 37 条

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5-aminolaevulinic acid and photodynamic therapy reduce HSV-1 replication in HaCat cells through an apoptosis-independent mechanism [J].