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Identifying targets for topical RNAi therapeutics in psoriasis: assessment of a new in vitro psoriasis model

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Abstract
Diseases of the skin are amenable to RNAi-based therapies and targeting key components in the pathophysiology of psoriasis using RNAi may represent a successful new therapeutic strategy. We aimed to develop a straightforward and highly reproducible in vitro psoriasis model useful to study the effects of gene knockdown by RNAi and to identify new targets for topical RNAi therapeutics. We evaluated the use of keratinocytes derived from psoriatic plaques and normal human keratinocytes (NHKs). To induce a psoriatic phenotype in NHKs, combinations of pro-inflammatory cytokines (IL-1 alpha, IL-17A, IL-6 and TNF-alpha) were tested. The model based on NHK met our needs of a reliable and predictive preclinical model, and this model was further selected for gene expression analyses, comprising a panel of 55 psoriasis-associated genes and five micro-RNAs (miRNAs). Gene silencing studies were conducted by using small interfering RNAs (siRNAs) and miRNA inhibitors directed against potential target genes such as CAMP and DEFB4 and miRNAs such as miR-203. We describe a robust and highly reproducible in vitro psoriasis model that recapitulates expression of a large panel of genes and miRNAs relevant to the pathogenesis of psoriasis. Furthermore, we show that our model is a powerful first step model system for testing and screening RNAi-based therapeutics.
Keywords
In vitro model, Psoriasis, RNA interference, siRNA, miRNA, CULTURED HUMAN KERATINOCYTES, INNATE IMMUNE-RESPONSES, ANTIMICROBIAL PEPTIDE, SKIN, DIFFERENTIATION, DRUGS, MECHANISMS, EXPRESSION, CELLS, HYPERPROLIFERATION

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Chicago
BRACKE, STEFANIE, Eline Desmet, Sara Guerrero-Aspizua, Sandra G Tjabringa, Joost Schalkwijk, Mireille Van Gele, Marta Carretero, and Jo Lambert. 2013. “Identifying Targets for Topical RNAi Therapeutics in Psoriasis: Assessment of a New in Vitro Psoriasis Model.” Archives of Dermatological Research 305 (6): 501–512.
APA
BRACKE, S., Desmet, E., Guerrero-Aspizua, S., Tjabringa, S. G., Schalkwijk, J., Van Gele, M., Carretero, M., et al. (2013). Identifying targets for topical RNAi therapeutics in psoriasis: assessment of a new in vitro psoriasis model. ARCHIVES OF DERMATOLOGICAL RESEARCH, 305(6), 501–512.
Vancouver
1.
BRACKE S, Desmet E, Guerrero-Aspizua S, Tjabringa SG, Schalkwijk J, Van Gele M, et al. Identifying targets for topical RNAi therapeutics in psoriasis: assessment of a new in vitro psoriasis model. ARCHIVES OF DERMATOLOGICAL RESEARCH. 2013;305(6):501–12.
MLA
BRACKE, STEFANIE, Eline Desmet, Sara Guerrero-Aspizua, et al. “Identifying Targets for Topical RNAi Therapeutics in Psoriasis: Assessment of a New in Vitro Psoriasis Model.” ARCHIVES OF DERMATOLOGICAL RESEARCH 305.6 (2013): 501–512. Print.
@article{4090605,
  abstract     = {Diseases of the skin are amenable to RNAi-based therapies and targeting key components in the pathophysiology of psoriasis using RNAi may represent a successful new therapeutic strategy. We aimed to develop a straightforward and highly reproducible in vitro psoriasis model useful to study the effects of gene knockdown by RNAi and to identify new targets for topical RNAi therapeutics. We evaluated the use of keratinocytes derived from psoriatic plaques and normal human keratinocytes (NHKs). To induce a psoriatic phenotype in NHKs, combinations of pro-inflammatory cytokines (IL-1 alpha, IL-17A, IL-6 and TNF-alpha) were tested. The model based on NHK met our needs of a reliable and predictive preclinical model, and this model was further selected for gene expression analyses, comprising a panel of 55 psoriasis-associated genes and five micro-RNAs (miRNAs). Gene silencing studies were conducted by using small interfering RNAs (siRNAs) and miRNA inhibitors directed against potential target genes such as CAMP and DEFB4 and miRNAs such as miR-203. We describe a robust and highly reproducible in vitro psoriasis model that recapitulates expression of a large panel of genes and miRNAs relevant to the pathogenesis of psoriasis. Furthermore, we show that our model is a powerful first step model system for testing and screening RNAi-based therapeutics.},
  author       = {BRACKE, STEFANIE and Desmet, Eline and Guerrero-Aspizua, Sara and Tjabringa, Sandra G and Schalkwijk, Joost and Van Gele, Mireille and Carretero, Marta and Lambert, Jo},
  issn         = {0340-3696},
  journal      = {ARCHIVES OF DERMATOLOGICAL RESEARCH},
  language     = {eng},
  number       = {6},
  pages        = {501--512},
  title        = {Identifying targets for topical RNAi therapeutics in psoriasis: assessment of a new in vitro psoriasis model},
  url          = {http://dx.doi.org/10.1007/s00403-013-1379-9},
  volume       = {305},
  year         = {2013},
}

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