Interaction of Wnt5a with Notch1 is Critical for the Pathogenesis of Psoriasis.
- Author:
Jeong Eun KIM
1
;
Seung Hyun BANG
;
Jee Ho CHOI
;
Chang Deok KIM
;
Chong Hyun WON
;
Mi Woo LEE
;
Sung Eun CHANG
Author Information
- Publication Type:Original Article
- Keywords: Notch1; Psoriasis; Wnt5a
- MeSH: Biopsy; Humans; Interferon-gamma; Interleukin-12; Interleukins; Keratinocytes; Psoriasis*; Skin; Tumor Necrosis Factor-alpha
- From:Annals of Dermatology 2016;28(1):45-54
- CountryRepublic of Korea
- Language:English
- 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-1alpha, TNF-alpha, transforming growth factor-alpha, and interferon-gamma downregulated Notch1 as well as HES 1, 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.
