Interaction of Wnt5a with Notch1 is Critical for the Pathogenesis of Psoriasisopen access
- Authors
- Kim, Jeong Eun; Bang, Seung Hyun; Choi, Jee Ho; Kim, Chang Deok; Won, Chong Hyun; Lee, Mi Woo; Chang, Sung Eun
- Issue Date
- Feb-2016
- Publisher
- KOREAN DERMATOLOGICAL ASSOC
- Keywords
- Notch1; Psoriasis; Wnt5a
- Citation
- ANNALS OF DERMATOLOGY, v.28, no.1, pp.45 - 54
- Indexed
- SCIE
SCOPUS
KCI
- Journal Title
- ANNALS OF DERMATOLOGY
- Volume
- 28
- Number
- 1
- Start Page
- 45
- End Page
- 54
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/155163
- DOI
- 10.5021/ad.2016.28.1.45
- ISSN
- 1013-9087
- Abstract
- Background: Psoriasis is characterized by uncontrolled hyperproliferation, aberrant differentiation, and dermal infiltration of immune cells. Recent studies have reported that Wnt5a and Notch1 signaling are altered in psoriatic skin lesions. Objective: We aimed to investigate the interaction of Wnt5a with Notch 1 with respect to inflammation-mediated epidermal hyperproliferation in psoriasis. Methods: Expression of Wnt5a and Notch1 signaling-related proteins were examined in psoriatic skin biopsies. Wnt5a was upregulated in human keratinocytes by treating the cells with its recombinant form (rWnt5a). Results: In psoriatic lesions, expression of Wnt5a increased while that of Notch1 decreased when compared to that in non-lesional and normal skin. Treatment with rWnt5a increased the proliferation of keratinocytes and increased their secretion of interleukin (IL)-23, IL-12, and tumor necrosis factor (TNF)-alpha. Further, exposure of keratinocytes to IL-1 alpha, TNF-alpha, transforming growth factor-alpha, and interferon-gamma downregulated Notch1 as well as HES1, which is downstream to Notch1, but increased the Wnt5a levels. The upregulated Wnt5a in keratinocytes downregulated both Notch1 and HES1. Conclusion: Our data suggest that Wnt5a and Notch1 signaling exert counteracting influences on each other and are involved, in part, in the pathomechanism of psoriasis.
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