title: In a three-dimensional reconstructed human epidermis filaggrin-2 is essential for proper cornification.
abstract: Atopic dermatitis is a chronic inflammatory skin disease with defects in the epidermal barrier. In a cohort of African-American children, a FLG2 nonsense mutation has been associated with the disease. In the epidermis of European patients, the expression of filaggrin-2, the filaggrin-related protein encoded by FLG2, is decreased. To describe the function of filaggrin-2 and evaluate the impact of its deficiency, its expression was downregulated using lentivirus-mediated shRNA interference in a three-dimensional reconstructed human epidermis (RHE) model. This resulted in parakeratosis and a compact stratum corneum, presence of abnormal vesicles inside the corneocytes, increased pH and reduced amounts of free amino acids at the RHE surface, leading to increased sensitivity to UVB radiations. The expression of differentiation markers was slightly modified. However, we observed reduced proteolytic processing of corneodesmosin, hornerin and filaggrin in parallel with reduced amounts of caspase-14 and bleomycin hydrolase. Our data demonstrated that filaggrin-2 is important for a proper cornification and a functional stratum corneum. Its downregulation in atopic patients may be involved in the disease-associated epidermis impairment.
authors.affiliation: 1] UMR5165 CNRS, CHU Purpan, Place du Dr Baylac TSA40031, 31059 Toulouse CEDEX 9, France [2] U1056 INSERM, CHU Purpan, Place du Dr Baylac TSA40031, 31059 Toulouse CEDEX 9, France [3] University of Toulouse, CHU Purpan, Place du Dr Baylac TSA40031, 31059 Toulouse CEDEX 9, France.
authors.forename: V
authors.initials: V
authors.lastname: Pendaries
authors.affiliation: 1] UMR5165 CNRS, CHU Purpan, Place du Dr Baylac TSA40031, 31059 Toulouse CEDEX 9, France [2] U1056 INSERM, CHU Purpan, Place du Dr Baylac TSA40031, 31059 Toulouse CEDEX 9, France [3] University of Toulouse, CHU Purpan, Place du Dr Baylac TSA40031, 31059 Toulouse CEDEX 9, France.
authors.forename: M
authors.initials: M
authors.lastname: Le Lamer
authors.affiliation: 1] UMR5165 CNRS, CHU Purpan, Place du Dr Baylac TSA40031, 31059 Toulouse CEDEX 9, France [2] U1056 INSERM, CHU Purpan, Place du Dr Baylac TSA40031, 31059 Toulouse CEDEX 9, France [3] University of Toulouse, CHU Purpan, Place du Dr Baylac TSA40031, 31059 Toulouse CEDEX 9, France.
authors.forename: L
authors.initials: L
authors.lastname: Cau
authors.affiliation: Department of Dermatology, University Hospital of Schleswig-Holstein, Schittenhelmstrasse 7, 24105 Kiel, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Hansmann
authors.affiliation: Cell and Tissue Laboratory, URPHYM-NARILIS, University of Namur, Rue de Bruxelles, 61, 5000 Namur, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Malaisse
authors.affiliation: Academic Medical Center, Coronel Institute of Occupational Health, PO Box 22 700, 1100 DE Amsterdam, The Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: Kezic
authors.affiliation: 1] UMR5165 CNRS, CHU Purpan, Place du Dr Baylac TSA40031, 31059 Toulouse CEDEX 9, France [2] U1056 INSERM, CHU Purpan, Place du Dr Baylac TSA40031, 31059 Toulouse CEDEX 9, France [3] University of Toulouse, CHU Purpan, Place du Dr Baylac TSA40031, 31059 Toulouse CEDEX 9, France.
authors.forename: G
authors.initials: G
authors.lastname: Serre
authors.affiliation: 1] UMR5165 CNRS, CHU Purpan, Place du Dr Baylac TSA40031, 31059 Toulouse CEDEX 9, France [2] U1056 INSERM, CHU Purpan, Place du Dr Baylac TSA40031, 31059 Toulouse CEDEX 9, France [3] University of Toulouse, CHU Purpan, Place du Dr Baylac TSA40031, 31059 Toulouse CEDEX 9, France.
authors.forename: M
authors.identifier: 0000000336556329
authors.initials: M
authors.lastname: Simon
mesh_terms: D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002478:Cells, Cultured; D004817:Epidermis / Q000378:metabolism*; D000091344:Filaggrin Proteins; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007381:Intermediate Filament Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D009418:S100 Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C109656:CDSN protein, human; D002135:Calcium-Binding Proteins; C000717249:FLG protein, human; C000717250:FLG2 protein, human; D000091344:Filaggrin Proteins; D006023:Glycoproteins; C503908:HRNR protein, human; D036341:Intercellular Signaling Peptides and Proteins; D007381:Intermediate Filament Proteins; D009418:S100 Proteins