Functional analysis of RIP1 using 3D cultured epidermal model - Is 'keratosis' a necroptosis? -
Project/Area Number |
15K19669
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Dermatology
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Research Institution | Asahikawa Medical College |
Principal Investigator |
SAITO Nao 旭川医科大学, 医学部, 研究生 (90736670)
|
Project Period (FY) |
2015-04-01 – 2017-03-31
|
Project Status |
Completed (Fiscal Year 2016)
|
Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
|
Keywords | RIP1 / 尋常性乾癬 |
Outline of Final Research Achievements |
Receptor-interacting protein kinase 1 (RIP1) regulate inflammatory signaling in response to stimuli, such as TNF-α, TRAIL, and TLRs, resulting in apoptosis, necroptosis and NF-κB activation. However, the physiological relevance in human epidermis remains elusive. In this study, we examined whether RIP1 is involved in the pathogenesis of psoriasis. In lesional psoriatic epidermis, RIP1-expression was decreased compared with normal epidermis. In addition, RIP1-knockdown enhanced TRAIL-mediated expression of psoriasis-related cytokines, such as IL-1β, IL-6, IL-8, TNF-α, in HEK. Moreover, TRAIL-neutralization in an imiquimod-induced murine psoriasis model remarkably improved skin phenotype, such as ear thickness, and TNF-α expression in lesional skin. Collecting these results, we conclude that TRAIL-mediated downregulation of RIP1 plays a critical role in the pathogenesis of psoriasis vulgaris via positive regulation of psoriasis-related cytokine-expression.
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Report
(3 results)
Research Products
(2 results)