Filaggrin Expression and Processing Deficiencies Impair Corneocyte Surface Texture and Stiffness in Mice.

Autor:	Thyssen JP; Department of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark. Electronic address: jacob.p.thyssen@regionh.dk., Jakasa I; Laboratory for Analytical Chemistry, Department of Chemistry and Biochemistry, Faculty of Food Technology and Biotechnology, University of Zagreb, Zagreb, Croatia., Riethmüller C; Serend-ip GmbH, Centre for Nanotechnology, Munster, Germany., Schön MP; Department of Dermatology, Venereology, and Allergology, University Medical Center, Georg August University, Göttingen, Germany; Lower Saxony Institute of Occupational Dermatology, University Medical Center, Göttingen, Germany., Braun A; Department of Dermatology, Venereology, and Allergology, University Medical Center, Georg August University, Göttingen, Germany; Lower Saxony Institute of Occupational Dermatology, University Medical Center, Göttingen, Germany., Haftek M; CNRS UMR5305, Laboratory of Tissue Biology and Therapeutic Engineering, Lyon, France., Fallon PG; School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland., Wróblewski J; Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers-New Jersey Medical School, International Center for Public Health, Newark, New Jersey; Institute of Biorganic Chemistry, Polish Academy of Science, Poznań, Poland., Jakubowski H; Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers-New Jersey Medical School, International Center for Public Health, Newark, New Jersey; Department of Biochemistry and Biotechnology, University of Life Sciences, Poznań, Poland., Eckhart L; Research Division of Biology and Pathobiology of the Skin, Department of Dermatology, Medical University of Vienna, Vienna, Austria., Declercq W; Molecular Signaling and Cell Death Unit, VIB-UGent Center for Inflammation Research, Technologiepark 927, Gent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium., Koppes S; Amsterdam UMC, University of Amsterdam, Coronel Institute of Occupational Health, Amsterdam Public Health research institute, Amsterdam, Netherlands., Engebretsen KA; Department of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark., Bonefeld C; Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark., Irvine AD; Paediatric Dermatology, Our Lady's Children's Hospital Crumlin, Dublin, Ireland; National Children's Research Centre, Our Lady's Children's Hospital Crumlin, Dublin, Ireland; Clinical Medicine, Trinity College Dublin, Dublin, Ireland., Keita-Alassane S; Laboratory for Epithelial Differentiation and Rheumatoid Autoimmunity, Inserm U1056, University of Toulouse III, Toulouse, France., Simon M; Laboratory for Epithelial Differentiation and Rheumatoid Autoimmunity, Inserm U1056, University of Toulouse III, Toulouse, France., Kawasaki H; Department of Dermatology, Keio University School of Medicine, Tokyo, Japan; Disease Biology group, Medical Sciences Innovation Hub Program, Cluster for Science and Technology Hub, RIKEN, Yokohama, Japans; Laboratory for Skin Homeostasis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan., Kubo A; Department of Dermatology, Keio University School of Medicine, Tokyo, Japan; Laboratory for Skin Homeostasis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan., Amagai M; Department of Dermatology, Keio University School of Medicine, Tokyo, Japan; Laboratory for Skin Homeostasis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan., Matsui T; Laboratory for Skin Homeostasis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan., Kezic S; Amsterdam UMC, University of Amsterdam, Coronel Institute of Occupational Health, Amsterdam Public Health research institute, Amsterdam, Netherlands. Electronic address: s.kezic@amc.uva.nl.
Jazyk:	angličtina
Zdroj:	The Journal of investigative dermatology [J Invest Dermatol] 2020 Mar; Vol. 140 (3), pp. 615-623.e5. Date of Electronic Publication: 2019 Aug 31.
DOI:	10.1016/j.jid.2019.07.716
Abstrakt:	Abundant corneocyte surface protrusions, observed in patients with atopic dermatitis with filaggrin loss-of-function mutations, are inversely associated with levels of natural moisturizing factors (NMFs) in the stratum corneum. To dissect the etiological role of NMFs and filaggrin deficiency in surface texture alterations, we examined mouse models with genetic deficiencies in the synthesis or degradation of filaggrin monomers for NMFs, cell stiffness (elastic modulus) and corneocyte surface protrusion density (dermal texture index). Five neonatal and adult mouse models carrying inactivating mutations of SASPase (Sasp -/- ), filaggrin (Flg ft/ft and Flg -/- ), filaggrin-hornerin (FlgHrnr -/- ), and bleomycin hydrolase (Blmh -/- ) were investigated. Sasp -/- and Flg -/- were on the hairless mouse background. Atomic force microscopy was used to determine elastic modulus and dermal texture index. Corneocytes of each neonatal as well as hairless adult knockout mouse exhibited an increased number of protrusions and decreased elastic modulus. In these mice, NMFs were reduced except for Sasp -/- . Dermal texture index was inversely correlated with NMFs and elastic modulus. Our findings demonstrate that any filaggrin-NMF axis deficiency can affect corneocyte mechanical properties in mice and likely in humans. Differences in NMFs and corneocyte surface texture between neonatal and adult as well as hairless and hairy mice emphasize the need for carefully selecting the most appropriate animal models for studies. (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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