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- Title
Psoriasin (S100A7) promotes stress-induced angiogenesis.
- Authors
Vegfors, J.; Ekman, A. ‐ K.; Stoll, S.W.; Bivik Eding, C.; Enerbäck, C.
- Abstract
Background Vascular modifications occur early in the development of psoriasis, and angiogenesis is one of the key features in the pathogenesis of the disease. Objectives To identify the role of the S100 protein psoriasin in psoriasis-associated angiogenesis. Methods The role of psoriasin in mediating angiogenesis was investigated by silencing psoriasin with small interfering RNA (si RNA) 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. Results Reactive oxygen species ( ROS) and hypoxia induced the expression of psoriasin. Downregulation of psoriasin in keratinocytes using si RNA altered the ROS-induced expression of the psoriasis-associated angiogenic factors vascular endothelial growth factor ( VEGF), heparin-binding epidermal growth factor-like growth factor, matrix metalloproteinase 1 and thrombospondin 1. Overexpression of psoriasin altered several regulators of angiogenesis and led to the secretion of psoriasin. Treatment with extracellular psoriasin induced proliferation, migration and tube formation in dermal-derived endothelial cells to a similar extent as VEGF and interleukin-17, and induced the expression and release of proangiogenic mediators. These effects were suggested to be mediated by the PI3K and nuclear factor kappa B pathways. Conclusions 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 angiogenesis.
- Subjects
NEOVASCULARIZATION; PSORIASIS; OXIDATIVE stress; BLOOD-vessel development; SKIN diseases
- Publication
British Journal of Dermatology, 2016, Vol 175, Issue 6, p1263
- ISSN
0007-0963
- Publication type
Article
- DOI
10.1111/bjd.14718