Barrier Function of the Skin: “La Raison d'Être” of the Epidermis

Abstract

The primary function of the epidermis is to produce the protective, semi-permeable stratum corneum that permits terrestrial life. The barrier function of the stratum corneum is provided by patterned lipid lamellae localized to the extracellular spaces between corneocytes. Anucleate corneocytes contain keratin filaments bound to a peripheral cornified envelope composed of cross-linked proteins. The many layers of these specialized cells in the stratum corneum provide a tough and resilient framework for the intercellular lipid lamellae. The lamellae are derived from disk-like lipid membranes extruded from lamellar granules into the intercellular spaces of the upper granular layer. Lysosomal and other enzymes present in the extracellular compartment are responsible for the lipid remodeling required to generate the barrier lamellae as well as for the reactions that result in desquamation. Lamellar granules likely originate from the Golgi apparatus and are currently thought to be elements of the tubulo-vesicular trans-Golgi network. The regulation of barrier lipid synthesis has been studied in a variety of models, with induction of several enzymes demonstrated during fetal development and keratinocyte differentiation, but an understanding of this process at the molecular genetic level awaits further study. Certain genetic defects in lipid metabolism or in the protein components of the stratum corneum produce scaly or ichthyotic skin with abnormal barrier lipid structure and function. The inflammatory skin diseases psoriasis and atopic dermatitis also show decreased barrier function, but the underlying mechanisms remain under investigation. Topically applied "moisturizers" work by acting as humectants or by providing an artificial barrier to trans-epidermal water loss; current work has focused on developing a more physiologic mix of lipids for topical application to skin. Recent studies in genetically engineered mice have suggested an unexpected role for tight junctions in epidermal barrier function and further developments in this area are expected. Ultimately, 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.

Revised nomenclature and classification of inherited ichthyoses: Results of the First Ichthyosis Consensus Conference in Sorèze 2009

“…The SC provides a barrier, which abruptly impedes the outward movement of interstitial fluid at the SG/SC interface, [153][154][155][156] and is formed by a series of highly hydrophobic lipid lamellae deposited through secretion of LB contents at the SG/SC interface between a mechanically resilient, yet pliable, scaffold of corneocytes. 157,158 In recent years, it has become evident that this most critical SC functionethe permeability barriereis impaired in most ichthyosis forms.…”

The effect of slurry on skin permeability to methylene blue dye in dairy cows with and without a history of digital dermatitis

“…However, the most important layer of the skin for maintaining the skin's barrier function is the stratum corneum (Madison, 2003), which is composed of 'dead' cells called corneocytes filled with keratin (Ersser et al, 2005). As the stratum corneum cells are 'dead' even in vivo, postmortem samples of human, pig and cattle tissues are frequently used as a model for live human tissue in pharmaceutical studies examining skin permeability (Pitman and Rostas, 1982;Netzlaff et al, 2006).…”

“…The mammalian skin acts as a protective barrier for the body by preventing the entry of pathogens and protecting against physical and chemical damage (Proksch et al, 2008). The most important layer of the skin in maintaining this barrier function is the outer layer, the stratum corneum (Madison, 2003). How well the skin functions as a barrier varies between individuals and could be affected by a number of factors including the -E-mail: maeve.palmer@afbini.gov.uk thickness of the stratum corneum (Holbrook and Odland, 1974), the number of hair follicles in the skin (Wosicka and Cal, 2010) and genetic mutations (Palmer et al, 2008).…”

Fetal and neonatal gene therapy: benefits and pitfalls

“…41 The barrier function of the skin has been described as the 'raison d'être' of the epidermis. 42 In mice, intra-amniotic injection of lacZ adenovirus resulted in skin expression, which decreased the later in gestation the injection was performed. 43 Similarly, neonatal, but not adult muscle, was found to strongly express b-galactosidase after delivery by herpex simplex virus vector.…”