Journal ArticleDOI
The skin: an indispensable barrier
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
More filters
Journal ArticleDOI
The role of filaggrin in the skin barrier and disease development
TL;DR: The present article reviews the current knowledge on the role of filaggrin in the skin barrier, FLG mutations, and the consequences of filggrin deficiency.
Journal ArticleDOI
Serum response factor is essential for the proper development of skin epithelium
TL;DR: The results demonstrate that Srf is essential for the actin-mediated sealing of epithelial cell-cell contacts and the development of functional stratified skin epithelium in vivo.
Journal ArticleDOI
Physicochemical and biopharmaceutical aspects influencing skin permeation and role of SLN and NLC for skin drug delivery
Eliana B. Souto,Joana F. Fangueiro,Ana Fernandes,Amanda Cano,Elena Sánchez-López,Maria L. Garcia,Patrícia Severino,Maria Ondina Paganelli,Marco Vinícius Chaud,Amélia M. Silva +9 more
TL;DR: In this article , the physicochemical and biopharmaceutical aspects encountered in the pathway of drugs through the skin, and the potential added value of using solid lipid nanoparticles (SLN) and nanostructured lipid vectors (NLC) to drug permeation/penetration through this route.
Journal ArticleDOI
Nanomedicines to Treat Skin Pathologies with Natural Molecules
TL;DR: It is suggested that the application of natural molecules onto the skin by lipid-based nanosystems can provide numerous clinician benefits in dermatology and cosmetics.
Journal ArticleDOI
Mechanical Tomography of Human Corneocytes with a Nanoneedle
TL;DR: The small diameter of the nanoneedle allows this "mechanical tomography" to be performed with high spatial resolution, potentially offering an opportunity to detect biomechanical changes in corneocytes because of, e.g., environmental factors, aging, or dermatological pathologies.
References
More filters
Journal ArticleDOI
Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis
Colin N. A. Palmer,Alan D. Irvine,Ana Terron-Kwiatkowski,Yiwei Zhao,Haihui Liao,Simon P. Lee,David Goudie,Aileen Sandilands,Linda E. Campbell,Frances J.D. Smith,Grainne M. O'Regan,Rosemarie Watson,Jo E Cecil,Sherri J. Bale,John G. Compton,John J. DiGiovanna,John J. DiGiovanna,Philip Fleckman,Sue Lewis-Jones,Gehan Arseculeratne,Ann Sergeant,Colin S. Munro,Brahim El Houate,Ken McElreavey,Liselotte Brydensholt Halkjaer,Hans Bisgaard,Somnath Mukhopadhyay,Somnath Mukhopadhyay,W.H. Irwin McLean +28 more
TL;DR: It is shown that two independent loss-of-function genetic variants (R510X and 2282del4) in the gene encoding filaggrin (FLG) are very strong predisposing factors for atopic dermatitis.
Journal ArticleDOI
The cornified envelope: a model of cell death in the skin
TL;DR: New insights into the molecular mechanisms and the physiological endpoints of cornification are increasing the understanding of the pathological defects of this unique form of programmed cell death, which is associated with barrier malfunctions and ichthyosis.
Journal ArticleDOI
Claudin-based tight junctions are crucial for the mammalian epidermal barrier a lesson from claudin-1–deficient mice
Mikio Furuse,Masaki Hata,Kyoko Furuse,Yoko Yoshida,Akinori Haratake,Yoshinobu Sugitani,Tetsuo Noda,Tetsuo Noda,Akiharu Kubo,Shoichiro Tsukita +9 more
TL;DR: Findings provide the first evidence that continuous claudin-based TJs occur in the epidermis and that these TJs are crucial for the barrier function of the mammalian skin.
Journal ArticleDOI
Claudins and epithelial paracellular transport.
TL;DR: Information is reviewed on the structure, function, and transcriptional and posttranslational regulation of the claudin family as well as of their evolutionarily distant relatives called the PMP22/EMP/MP20/claudin, or pfam00822, superfamily.
Journal ArticleDOI
Barrier Function of the Skin: “La Raison d'Être” of the Epidermis
TL;DR: More sophisticated understanding of epidermal barrier function will lead to more rational therapy of a host of skin conditions in which the barrier is impaired, current work has focused on developing a more physiologic mix of lipids for topical application to skin.
Related Papers (5)
Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis
Colin N. A. Palmer,Alan D. Irvine,Ana Terron-Kwiatkowski,Yiwei Zhao,Haihui Liao,Simon P. Lee,David Goudie,Aileen Sandilands,Linda E. Campbell,Frances J.D. Smith,Grainne M. O'Regan,Rosemarie Watson,Jo E Cecil,Sherri J. Bale,John G. Compton,John J. DiGiovanna,John J. DiGiovanna,Philip Fleckman,Sue Lewis-Jones,Gehan Arseculeratne,Ann Sergeant,Colin S. Munro,Brahim El Houate,Ken McElreavey,Liselotte Brydensholt Halkjaer,Hans Bisgaard,Somnath Mukhopadhyay,Somnath Mukhopadhyay,W.H. Irwin McLean +28 more