title: The desmosomal protein desmoglein 1 aids recovery of epidermal differentiation after acute UV light exposure.
abstract: Epidermal structure is damaged by exposure to UV light, but the molecular mechanisms governing structural repair are largely unknown. UVB (290-320 nm wavelengths) exposure before induction of differentiation reduced expression of differentiation-associated proteins, including desmoglein 1 (Dsg1), desmocollin 1 (Dsc1), and keratins 1 and 10 (K1/K10), in a dose-dependent manner in normal human epidermal keratinocytes (NHEKs). The UVB-induced reduction in both Dsg1 transcript and protein was associated with reduced binding of the p63 transcription factor to previously unreported enhancer regulatory regions of the Dsg1 gene. As Dsg1 promotes epidermal differentiation in addition to participating in cell-cell adhesion, the role of Dsg1 in aiding differentiation after UVB damage was tested. Compared with controls, depleting Dsg1 via short hairpin RNA resulted in further reduction of Dsc1 and K1/K10 expression in monolayer NHEK cultures and in abnormal epidermal architecture in organotypic skin models recovering from UVB exposure. Ectopic expression of Dsg1 in keratinocyte monolayers rescued the UVB-induced differentiation defect. Treatment of UVB-exposed monolayer or organotypic cultures with trichostatin A, a histone deacetylase inhibitor, partially restored differentiation marker expression, suggesting a potential therapeutic strategy for reversing UV-induced impairment of epidermal differentiation after acute sun exposure.
authors.affiliation: Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA; Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
authors.forename: Jodi L
authors.initials: JL
authors.lastname: Johnson
authors.affiliation: Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Koetsier
authors.affiliation: CEINGE Biotecnologie Avanzate, Napoli, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Sirico
authors.affiliation: Department of Chemistry, Spelman College, Atlanta, Georgia, USA.
authors.forename: Ada T
authors.initials: AT
authors.lastname: Agidi
authors.affiliation: CEINGE Biotecnologie Avanzate, Napoli, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Antonini
authors.affiliation: CEINGE Biotecnologie Avanzate, Napoli, Italy; Department of Biology, University of Naples Federico II, Napoli, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Missero
authors.affiliation: Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA; Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. Electronic address: kgreen@northwestern.edu.
authors.forename: Kathleen J
authors.initials: KJ
authors.lastname: Green
mesh_terms: D002454:Cell Differentiation; D002478:Cells, Cultured; D051183:Desmoglein 1 / Q000235:genetics / Q000502:physiology*; D000078404:Epidermal Cells; D004817:Epidermis / Q000528:radiation effects*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D014466:Ultraviolet Rays
chemical_list: D051183:Desmoglein 1; D006877:Hydroxamic Acids; D012333:RNA, Messenger; C012589:trichostatin A