title: Psoriasin (S100A7) promotes stress-induced angiogenesis.
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.
  
  
  OBJECTIVE
  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 (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.
  
  
  RESULTS
  Reactive oxygen species (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 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.
authors.affiliation: Department of Clinical and Experimental Medicine, Ingrid Asp Psoriasis Research Center, Linköping University, Linköping, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Vegfors
authors.affiliation: Department of Clinical and Experimental Medicine, Ingrid Asp Psoriasis Research Center, Linköping University, Linköping, Sweden.
authors.forename: A-K
authors.initials: AK
authors.lastname: Ekman
authors.affiliation: Department of Dermatology, University of Michigan, Ann Arbor, MI, U.S.A.
authors.forename: S W
authors.initials: SW
authors.lastname: Stoll
authors.affiliation: Department of Clinical and Experimental Medicine, Ingrid Asp Psoriasis Research Center, Linköping University, Linköping, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Bivik Eding
authors.affiliation: Department of Clinical and Experimental Medicine, Ingrid Asp Psoriasis Research Center, Linköping University, Linköping, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Enerbäck
mesh_terms: D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide; D015603:Keratinocytes / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000209:etiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011565:Psoriasis / Q000473:pathology; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins / Q000502:physiology*; D012867:Skin / Q000378:metabolism; D013312:Stress, Physiological / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology
chemical_list: D016328:NF-kappa B; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; C089242:S100A7 protein, human; D006861:Hydrogen Peroxide; D019869:Phosphatidylinositol 3-Kinases; D040262:Receptors, Vascular Endothelial Growth Factor