title: Interaction of Wnt5a with Notch1 is Critical for the Pathogenesis of Psoriasis.
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)-α. Further, exposure of keratinocytes to IL-1α, TNF-α, transforming growth factor-α, and interferon-γ 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.
  
  
  CONCLUSIONS
  Our data suggest that Wnt5a and Notch1 signaling exert counteracting influences on each other and are involved, in part, in the pathomechanism of psoriasis.
authors: Department of Dermatology, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.; Department of Dermatology, Hanyang University Hospital, Hanyang University College of Medicine, Seoul, Korea.
authors: Jeong Eun
authors: JE
authors: Kim
authors: Department of Dermatology, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors: Seung Hyun
authors: SH
authors: Bang
authors: Department of Dermatology, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors: Jee Ho
authors: JH
authors: Choi
authors: Department of Dermatology, Chungnam National University College of Medicine, Daejeon, Korea.
authors: Chang Deok
authors: CD
authors: Kim
authors: Department of Dermatology, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors: Chong Hyun
authors: CH
authors: Won
authors: Department of Dermatology, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors: Mi Woo
authors: MW
authors: Lee
authors: Department of Dermatology, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors: Sung Eun
authors: SE
authors: Chang
keywords: Notch1; Psoriasis; Wnt5a