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Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome
Published on: June 15, 2016
Treating psoriasis by targeting its susceptibility gene Rel
Tingting Fan1, Shaowen Wang1, Linjiang Yu1
1Shenzhen Laboratory of Fully Human Antibody Engineering, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, People's Republic of China.
Abstract:
Psoriasis is a chronic inflammatory disorder of the skin. Accumulating evidence indicates that the Rel gene, a member of the NF-κB family, is a risk factor for the disease. We sought to investigate whether psoriasis can be prevented by directly targeting the Rel gene transcript, i.e., the c-Rel mRNA. Using chemically-modified c-Rel specific siRNA (siRel) and poly(ethylene glycol)-b-poly(l-lysine)-b-poly(l-leucine) (PEG-PLL-PLLeu) micelles, we successfully knocked down the expression of c-Rel, and showed that the expression of cytokine IL-23, a direct target of c-Rel that can drive the development of IL-17-producing T cells, was markedly inhibited. More importantly, treating mice with siRel not only prevented but also ameliorated imiquimod (IMQ)-induced psoriasis. Mechanistic studies showed that siRel treatment down-regulated the expression of multiple inflammatory cytokines. Taken together, these results indicate that the susceptibility gene Rel can be targeted to treat and prevent psoriasis.
Insights
Targeting the c-Rel mRNA with siRNA prevented and treated psoriasis in mice. This approach inhibited key inflammatory cytokines like IL-23, offering a new therapeutic strategy for this chronic skin condition.
Area of Science:
- Dermatology
- Immunology
- Molecular Biology
Background:
- Psoriasis is a chronic inflammatory skin disease.
- The Rel gene (a member of the NF-κB family) is implicated as a risk factor for psoriasis.
- Targeting the c-Rel mRNA presents a potential therapeutic avenue.
Purpose of the Study:
- To investigate the prevention and treatment of psoriasis by targeting the c-Rel mRNA.
- To evaluate the efficacy of c-Rel specific siRNA (siRel) in a mouse model of psoriasis.
Main Methods:
- Utilized chemically-modified c-Rel specific siRNA (siRel) encapsulated in PEG-PLL-PLLeu micelles.
- Assessed c-Rel gene knockdown and its effect on downstream targets like IL-23.
- Employed an imiquimod (IMQ)-induced mouse model to study psoriasis development and treatment.
Main Results:
- Successfully achieved knockdown of c-Rel expression using siRel.
- Demonstrated significant inhibition of IL-23 cytokine expression, a key driver of IL-17-producing T cells.
- Showed that siRel treatment prevented and ameliorated IMQ-induced psoriasis in mice.
- Observed down-regulation of multiple inflammatory cytokines following siRel treatment.
Conclusions:
- Targeting the susceptibility gene Rel via its mRNA transcript is a viable strategy for psoriasis treatment and prevention.
- siRel effectively inhibits key inflammatory pathways involved in psoriasis pathogenesis.
- This study provides a foundation for developing novel RNA-based therapies for psoriasis.
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