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