Psoriasin (S100A7) promotes stress‐induced angiogenesis

J. Vegfors, A.‐K. Ekman, S.W. Stoll, C. Bivik Eding, C. Enerbäck

Vascular modifications occur early in the development of psoriasis and angiogenesis is one of the key features in the pathogenesis of the disease. We aimed to identify the role of the S100 protein psoriasin in the angiogenesis associated with psoriasis. The role of psoriasin in mediating angiogenesis was investigated by silencing psoriasin with siRNA and measuring psoriasis-associated angiogenic factors in human epidermal keratinocytes. The secretion of psoriasin and the effect of psoriasin on general regulators of angiogenesis in keratinocytes, and on endothelial cell migration, proliferation, tube formation and production of angiogenic mediators, was evaluated. The oxidative stress factors ROS and hypoxia induced the expression of psoriasin. Downregulation of psoriasin in keratinocytes using siRNA altered the ROS-induced expression of the psoriasis-associated angiogenic factors vascular endothelial growth factor (VEGF), heparin-binding EGF-like growth factor (HB-EGF), matrix metalloproteinase (MMP)-1 and thrombospondin (THBS)-1. Overexpression of psoriasin altered several regulators of angiogenesis and led to the secretion of psoriasin protein. Treatment with extracellular psoriasin induced proliferation, migration and tube formation in dermal-derived endothelial cells to a similar extent as VEGF and interleukin (IL)-17, and induced the expression and release of pro-angiogenic mediators. These effects were suggested to be mediated by the PI3K and NFκB pathways. These findings suggest that psoriasin expression is promoted by oxidative stress in keratinocytes and amplifies the ROS-induced expression of angiogenic factors relevant to psoriasis. Moreover, extracellularly secreted psoriasin may act on dermal endothelial cells to contribute to key features of the angiogenic process. This article is protected by copyright. All rights reserved.