title: ZEB2-transgene expression in the epidermis compromises the integrity of the epidermal barrier through the repression of different tight junction proteins.
abstract: Epithelial homeostasis within the epidermis is maintained by means of multiple cell-cell adhesion complexes such as adherens junctions, tight junctions, gap junctions, and desmosomes. These complexes co-operate in the formation and the regulation of the epidermal barrier. Disruption of the epidermal barrier through the deregulation of the above complexes is the cause behind a number of skin disorders such as psoriasis, dermatitis, keratosis, and others. During epithelial-to-mesenchymal transition (EMT), epithelial cells lose their adhesive capacities and gain mesenchymal properties. ZEB transcription factors are key inducers of EMT. In order to gain a better understanding of the functional role of ZEB2 in epidermal homeostasis, we generated a mouse model with conditional overexpression of Zeb2 in the epidermis. Our analysis revealed that Zeb2 expression in the epidermis leads to hyperproliferation due to the combined downregulation of different tight junction proteins compromising the epidermal barrier. Using two epidermis-specific in vivo models and in vitro promoter assays, we identified occludin as a new Zeb2 target gene. Immunohistological analysis performed on human skin biopsies covering various pathogeneses revealed ZEB2 expression in the epidermis of pemphigus vulgaris. Collectively, our data support the notion for a potential role of ZEB2 in intracellular signaling of this disease.
authors.affiliation: Unit of Molecular and Cellular Oncology, Inflammation Research Center, VIB, Technologiepark 927, 9052, Ghent (Zwijnaarde), Belgium.
authors.forename: Marianthi N
authors.initials: MN
authors.lastname: Tatari
authors.forename: Bram
authors.initials: B
authors.lastname: De Craene
authors.forename: Bieke
authors.initials: B
authors.lastname: Soen
authors.forename: Joachim
authors.initials: J
authors.lastname: Taminau
authors.forename: Petra
authors.initials: P
authors.lastname: Vermassen
authors.forename: Steven
authors.initials: S
authors.lastname: Goossens
authors.forename: Katharina
authors.initials: K
authors.lastname: Haigh
authors.forename: Silvia
authors.initials: S
authors.lastname: Cazzola
authors.forename: Jo
authors.initials: J
authors.lastname: Lambert
authors.forename: Danny
authors.initials: D
authors.lastname: Huylebroeck
authors.forename: Jody J
authors.initials: JJ
authors.lastname: Haigh
authors.forename: Geert
authors.initials: G
authors.lastname: Berx
mesh_terms: D000818:Animals; D002460:Cell Line; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D062793:Occludin / Q000378:metabolism; D010392:Pemphigus / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D019108:Tight Junctions / Q000378:metabolism*; D000074165:Zinc Finger E-box Binding Homeobox 2
chemical_list: D018398:Homeodomain Proteins; D062793:Occludin; D012097:Repressor Proteins; C492363:ZEB2 protein, human; C120602:ZEB2 protein, mouse; D000074165:Zinc Finger E-box Binding Homeobox 2