Journal ArticleDOI
The skin: an indispensable barrier
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TLDR
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.Abstract:
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 dermatitisread more
Citations
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The skin microbiome
TL;DR: An enhanced understanding of the skin microbiome is necessary to gain insight into microbial involvement in human skin disorders and to enable novel promicrobial and antimicrobial therapeutic approaches for their treatment.
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UV Radiation and the Skin
TL;DR: Developing UV-protective approaches based on a detailed understanding of molecular events that occur after UV exposure, focusing particularly on epidermal melanization and the role of the MC1R in genome maintenance are targeted.
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Titanium dioxide and zinc oxide nanoparticles in sunscreens: focus on their safety and effectiveness
TL;DR: Caution should still be exercised when new sunscreens are developed and research that includes sunscreen NP stabilization, chronic exposures, and reduction of NPs' free-radical production should receive full attention.
Journal ArticleDOI
Epidermal Barrier Dysfunction in Atopic Dermatitis
Michael J. Cork,Simon G. Danby,Yiannis Vasilopoulos,Jonathan Hadgraft,Majella E. Lane,Manar Moustafa,Manar Moustafa,Richard H. Guy,Alice Macgowan,Rachid Tazi-Ahnini,Simon J. Ward +10 more
TL;DR: The strong association between both genetic barrier defects and environmental insults to the barrier with AD suggests that epidermal barrier dysfunction is a primary event in the development of this disease.
References
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Journal ArticleDOI
Cathepsin D is involved in the regulation of transglutaminase 1 and epidermal differentiation.
Friederike Egberts,Michael Heinrich,Jens-Michael Jensen,Supandi Winoto-Morbach,Stephan Pfeiffer,Marc Wickel,Michael Schunck,Judith Steude,Paul Saftig,Ehrhardt Proksch,Stefan Schütze +10 more
TL;DR: A functional link between cathepsin D activation, transglutaminase 1 activity and protein expression of cornified envelope proteins during epidermal differentiation is suggested.
Journal ArticleDOI
Structural organization of cornified cell envelopes and alterations in inherited skin disorders.
TL;DR: It is revealed that abnormal cornified cell envelope synthesis is significantly involved in the pathophysiology of certain inherited keratodermas and reflects perturbations in the complex yet highly orderly process of cornification cell envelope formation in normal skin biology.
Journal ArticleDOI
The interleukin-6 cytokine system regulates epidermal permeability barrier homeostasis.
Xu-Ping Wang,Michael Schunck,Karl-Josef Kallen,Claudia Neumann,Christian Trautwein,Stefan Rose-John,Ehrhardt Proksch +6 more
TL;DR: The results indicate that the IL- 6 cytokine system, particularly transsignalling via the soluble IL-6R, is critically involved in barrier repair after skin injury.
Journal ArticleDOI
Basis for Improved Permeability Barrier Homeostasis Induced by PPAR and LXR Activators: Liposensors Stimulate Lipid Synthesis, Lamellar Body Secretion, and Post-Secretory Lipid Processing
Mao-Qiang Man,Eung Ho Choi,Matt Schmuth,Debra Crumrine,Yoshikazu Uchida,Peter M. Elias,Walter M. Holleran,Kenneth R. Feingold +7 more
TL;DR: Topical PPAR and LXR activators stimulate epidermal lipid synthesis, increase LB secretion, and accelerate extracellular lipid processing, providing additional mechanisms that further account for their ability to improve epidersmal permeability barrier homeostasis.
Journal ArticleDOI
Connexin 26 regulates epidermal barrier and wound remodeling and promotes psoriasiform response
Ali R. Djalilian,David M. McGaughey,Satyakam Patel,Eun Young Seo,Chenghua Yang,Jun Cheng,Melanija Tomić,Satrajit Sinha,Akemi Ishida-Yamamoto,Julia A. Segre +9 more
TL;DR: The results provide a molecular link between barrier acquisition in utero and epidermal remodeling after wounding and suggest that the most effective treatments for inflammatory skin disorders might concomitantly suppress the immune response and enhanceEpidermal differentiation to restore the barrier.
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