19043850 2008 11 28 2009 02 02
1600-0625 17 12 2008 Dec Experimental dermatology Exp. Dermatol. The skin: an indispensable barrier. 1063-72 The skin forms an effective barrier between the organism and the environment preventing invasion of pathogens and fending off chemical and physical assaults, as well as the unregulated loss of water and solutes. In this review we provide an overview of several components of the physical barrier, explaining how barrier function is regulated and altered in dermatoses. The physical barrier is mainly localized in the stratum corneum (SC) and consists of protein-enriched cells (corneocytes with cornified envelope and cytoskeletal elements, as well as corneodesmosomes) and lipid-enriched intercellular domains. The nucleated epidermis also contributes to the barrier through tight, gap and adherens junctions, as well as through desmosomes and cytoskeletal elements. During epidermal differentiation lipids are synthesized in the keratinocytes and extruded into the extracellular domains, where they form extracellular lipid-enriched layers. The cornified cell envelope, a tough protein/lipid polymer structure, resides below the cytoplasmic membrane on the exterior of the corneocytes. Ceramides A and B are covalently bound to cornified envelope proteins and form the backbone for the subsequent addition of free ceramides, free fatty acids and cholesterol in the SC. Filaggrin is cross-linked to the cornified envelope and aggregates keratin filaments into macrofibrils. Formation and maintenance of barrier function is influenced by cytokines, 3',5'-cyclic adenosine monophosphate and calcium. Changes in epidermal differentiation and lipid composition lead to a disturbed skin barrier, which allows the entry of environmental allergens, immunological reaction and inflammation in atopic dermatitis. A disturbed skin barrier is important for the pathogenesis of contact dermatitis, ichthyosis, psoriasis and atopic dermatitis. Department of Dermatology, University Hospitals of Schleswig-Holstein, Kiel, Germany. eproksch@dermatology.uni-kiel.de Proksch Ehrhardt E Brandner Johanna M JM Jensen Jens-Michael JM eng Journal Article Review
Denmark Exp Dermatol 9301549 IM Animals Cell Communication physiology Epidermis cytology physiology physiopathology Humans Intercellular Junctions physiology Models, Biological Permeability Signal Transduction physiology Skin Diseases metabolism physiopathology Skin Physiological Phenomena 107
2008 12 2 9 0 2009 2 3 9 0 2008 12 2 9 0 ppublish 19043850
17603506 2007 07 02 2007 09 06
1465-7392 9 7 2007 Jul Nature cell biology Nat. Cell Biol. p63: revving up epithelial stem-cell potential. 731-3 Blanpain Cédric C Fuchs Elaine E eng News
England Nat Cell Biol 100890575 0 Phosphoproteins 0 Protein Isoforms 0 Trans-Activators 0 Trp63 protein, mouse 0 Tumor Suppressor Protein p53 IM Animals Cell Differentiation Cell Proliferation Epidermis cytology embryology Epithelial Cells physiology Mice Mice, Knockout Phosphoproteins genetics physiology Protein Isoforms genetics physiology Stem Cells physiology Trans-Activators genetics physiology Tumor Suppressor Protein p53 genetics metabolism
2007 7 3 9 0 2007 9 7 9 0 2007 7 3 9 0 ppublish ncb0707-731 10.1038/ncb0707-731 17603506