P03 RSAD2 regulated by IRF1 contributes to keratinocyte hyperproliferation and skin inflammation in psoriasis via the TAK1/NF-κB axis
Year: 2024
Type: conference-abstract
Abstract: Background Radical SAM domain-containing 2 (RSAD2) plays a crucial role in the innate immune response and is associated with a variety of immune diseases. However, the expression and immunomodulatory role of RSAD2 in psoriasis have not been clarified. Objectives We sought to explore the role of RSAD2 in psoriasis and its molecular mechanisms. Methods Western blot, qRT-PCR, immunohistochemistry and immunofluorescence staining were used to detect the expression of RSAD2 in psoriatic lesions. Datasets from the GEO database were analysed to reveal the relationship between the expression of RSAD2 and the severity of psoriasis. RNA-seq analysis was performed to identify genes and pathways regulated by IRF1 or RSAD2. A dual-luciferase reporter assay and CUT&Tag were performed to detect the direct binding of interferon regulatory factor-1 (IRF1) to RSAD2. CCK8, EdU assays, flow cytometry, and ELISA were used to determine the role of RSAD2 in the psoriatic cell model. Western blot was performed to investigate the relationship between RSAD2 and the TAK1-mediated NF-κB signalling pathway. The IMQ-induced psoriasis-like mouse model was established for in vivo experiments. Results RSAD2 was significantly upregulated in psoriatic tissues and in psoriasis-like mouse epidermis, and its expression correlated positively with the severity of psoriasis. In M5-treated keratinocytes, RSAD2 promotes the proliferation and secretion of proinflammatory cytokines by activating TAK1-mediated NF-κB signalling pathway. IRF1 increased the expression of RSAD2 by binding to the RSAD2 promoter region and the function of RSAD2 in psoriasis is regulated by IRF1. Moreover, treatment of RSAD2 siRNA decreased epidermal hyperplasia and attenuated IMQ-induced psoriatic dermatitis. Conclusions Our study revealed that upregulation of RSAD2 contributes to keratinocyte hyperproliferation and skin inflammation in psoriasis and is positively correlated with the severity of psoriasis, and the effect of RSAD2 is regulated by IRF1. RSAD2 may be a potential biomarker and therapeutic target in psoriasis.
Source: British Journal of Dermatology
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W4405229670