title: Regulation of involucrin in psoriatic epidermal keratinocytes: the roles of ERK1/2 and GSK-3β.
abstract: Psoriasis, a common inflammatory skin disease, is characterized by epidermal hyperplasia, abnormal differentiation, angiogenesis, immune activation, and inflammation. Involucrin is an early terminal differentiation marker of epidermal keratinocytes. In this study, we determined the immunolocalization of involucrin in psoriatic lesions and normal skin of individuals without psoriasis by means of immunofluorescence (IF) assay. Furthermore, the regulation of involucrin by interleukin (IL)-13, IL-17A, endothelin (ET)-1, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ was investigated by Western blot. Extracellular regulate protein kinases 1/2 (ERK1/2) and glycogen syntheses kinase-3β (GSK-3β) inhibitors were also included to define the roles of these signals in the production of involucrin in both psoriatic and normal keratinocytes. In psoriatic lesional skin, involucrin was detected in the stratum spinosum, but not in the basal or the cornified layer. In normal skin, involucrin was restricted to the granular layer and the upper stratum spinosum. IL-13, IL-17A, ET-1, TNF-α, and IFN-γ up-regulate expression of involucrin in both psoriatic and normal keratinocytes. However, this effect was abolished by ERK1/2 and GSK-3β inhibitors. In conclusion, involucrin is up-regulated in psoriatic keratinocytes. IL-13, IL-17A, ET-1, TNF-α, and IFN-γ could increase involucrin protein levels in psoriatic and normal keratinocytes. The ERK1/2 and GSK-3β signaling pathways may play positive roles in regulating epidermal differentiation as observed in psoriasis.
authors.affiliation: Department of Dermatology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Jia-Qi
authors.initials: JQ
authors.lastname: Chen
authors.forename: Xiao-Yong
authors.initials: XY
authors.lastname: Man
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Jiong
authors.initials: J
authors.lastname: Zhou
authors.forename: Lilla
authors.initials: L
authors.lastname: Landeck
authors.forename: Sui-Qing
authors.initials: SQ
authors.lastname: Cai
authors.forename: Min
authors.initials: M
authors.lastname: Zheng
mesh_terms: D000328:Adult; D000368:Aged; D002454:Cell Differentiation / Q000187:drug effects; D019332:Endothelin-1 / Q000494:pharmacology; D004817:Epidermis / Q000473:pathology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D018793:Interleukin-13 / Q000494:pharmacology; D020381:Interleukin-17 / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011498:Protein Precursors / Q000378:metabolism*; D011565:Psoriasis / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D055815:Young Adult
chemical_list: D019332:Endothelin-1; D018793:Interleukin-13; D020381:Interleukin-17; D047428:Protein Kinase Inhibitors; D011498:Protein Precursors; D014409:Tumor Necrosis Factor-alpha; C032253:involucrin; D007371:Interferon-gamma; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D048049:Extracellular Signal-Regulated MAP Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D038362:Glycogen Synthase Kinase 3