title: Murine filaggrin-2 is involved in epithelial barrier function and down-regulated in metabolically induced skin barrier dysfunction.
abstract: The S100 fused-type proteins (SFTPs) are thought to be involved in the barrier formation and function of the skin. Mutations in the profilaggrin gene, one of the best investigated members of this family, are known to be the major risk factors for ichthyosis vulgaris and atopic dermatitis. Recently, we identified human filaggrin-2 as a new member of the SFTP family. To achieve further insight into its function, here the murine filaggrin-2 was analysed as a possible orthologue. The 5' and 3' ends of the mouse filaggrin-2 cDNA of the BALB/c strain were sequenced and confirmed an organization typical for SFTPs. Murine filaggrin-2 showed an expression pattern mainly in keratinizing epithelia in the upper cell layers on both mRNA and protein levels. The expression in cultured mouse keratinocytes was increased upon elevated Ca(2+)  levels. Immunoblotting experiments indicated an intraepidermal processing of the 250-kDa full-length protein. In metabolically (essential fatty acid-deficient diet) induced skin barrier dysfunction, filaggrin-2 expression was significantly reduced, whereas filaggrin expression was up-regulated. In contrast, mechanical barrier disruption with acetone treatment did not affect filaggrin-2 mRNA expression. These results suggest that filaggrin-2 may contribute to epidermal barrier function and its regulation differs, at least in parts, from that of filaggrin.
authors.affiliation: Department of Dermatology, University Hospital Schleswig-Holstein, Campus Kiel, Germany.
authors.forename: Britta
authors.initials: B
authors.lastname: Hansmann
authors.forename: Kerstin
authors.initials: K
authors.lastname: Ahrens
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Wu
authors.forename: Ehrhardt
authors.initials: E
authors.lastname: Proksch
authors.forename: Ulf
authors.initials: U
authors.lastname: Meyer-Hoffert
authors.forename: Jens-Michael
authors.initials: JM
authors.lastname: Schröder
mesh_terms: D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D002478:Cells, Cultured; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D003876:Dermatitis, Atopic / Q000209:etiology; D015536:Down-Regulation; D004817:Epidermis / Q000502:physiology*; D005228:Fatty Acids, Essential / Q000008:administration & dosage / Q000172:deficiency; D000091344:Filaggrin Proteins; D006801:Humans; D016112:Ichthyosis Vulgaris / Q000209:etiology; D007381:Intermediate Filament Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008812:Mice, Hairless; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D009418:S100 Proteins / Q000235:genetics; D012871:Skin Diseases / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology*
chemical_list: D017931:DNA Primers; D018076:DNA, Complementary; C000717249:FLG protein, human; C000717250:FLG2 protein, human; D005228:Fatty Acids, Essential; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D012333:RNA, Messenger; D009418:S100 Proteins