title: Overexpression of Psoriasin (S100A7) Contributes to Dysregulated Differentiation in Psoriasis.
abstract: Psoriasin, which is highly expressed in psoriasis, is encoded by a gene located within the epidermal differentiation complex. The aim of this study was to investigate the effect of endogenous psoriasin on disturbed keratinocyte differentiation in psoriasis. Immunohistochemical staining revealed a gradient of psoriasin expression in the psoriatic epidermis with highest expression in the suprabasal, differentiated layers. Induction of keratinocyte differentiation caused concurrent expression of psoriasin and the differentiation marker involucrin. The differentiation-induced psoriasin expression was found to be mediated by the protein kinase C pathway. The downregulation of psoriasin expression by small interfering RNA revealed that psoriasin mediates the expression of involucrin, desmoglein 1, transglutaminase 1 and CD24 in normal differentiation. The lentivirus-mediated overexpression of psoriasin, mimicking the psoriatic milieu, gave rise to an altered regulation of differentiation genes and an expression pattern reminiscent of that in psoriatic epidermis. These findings suggest that psoriasin contributes to the dysregulated differentiation process in the psoriasis epidermis.
authors.affiliation: Ingrid Asp Psoriasis Research Center, Department of Clinical and Experimental Medicine, Linköping University, SE-581 85 Linköping, Sweden.
authors.forename: Anna-Karin
authors.initials: AK
authors.lastname: Ekman
authors.forename: Jenny
authors.initials: J
authors.lastname: Vegfors
authors.forename: Cecilia Bivik
authors.initials: CB
authors.lastname: Eding
authors.forename: Charlotta
authors.initials: C
authors.lastname: Enerbäck
mesh_terms: D051927:CD24 Antigen / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D002454:Cell Differentiation; D002478:Cells, Cultured; D051183:Desmoglein 1 / Q000235:genetics / Q000378:metabolism; D004817:Epidermis / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism* / Q000473:pathology; D011493:Protein Kinase C / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D011565:Psoriasis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D034622:RNA Interference; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection; D011503:Transglutaminases / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D051927:CD24 Antigen; C497889:CD24 protein, human; C495297:DSG1 protein, human; D051183:Desmoglein 1; D011498:Protein Precursors; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; C089242:S100A7 protein, human; C032253:involucrin; D011503:Transglutaminases; C105804:transglutaminase 1; D011493:Protein Kinase C