Abstract
The outermost layer of the skin, the stratum corneum, is essential for the protective barrier functions of the skin. It results from the stacking of corneocytes, the dead flattened cells resulting from epidermal terminal differentiation of underlying living keratinocytes. The cornified lipid envelope, encapsulating corneocytes, and the extracellular mortar-like multilayered lipid matrix, called lamellae, are two crucial elements of the epidermal barrier. Stratum corneum extracellular lipids are mainly composed of ceramides, cholesterol and free fatty acids. Ceramides, and more specifically the epidermis specific ω-O-acylceramides, are essential for lipid-matrix organization into lamellae and formation of the corneocyte lipid envelope. Pathophysiological studies of inherited lipid metabolism disorders recently contributed to a better understanding of stratum corneum lipid metabolism. In the lab, our data from patients with Autosomal Recessive Congenital Ichthyosis and a murine knock-out model showed that the enzyme PNPLA1 is essential for the last step of synthesis of omega-O-acylceramides. Skin aging is a complex biological process caused by genetic and extrinsic factors e.g. sun exposure, smoke, and pollution. Aging skin is marked by a senescence-related decline in lipid and water content, which ultimately impairs epidermal barrier function. Thus, aged epidermis is prone to develop altered drug permeability, increased susceptibility to irritants contact dermatitis and severe xerosis. Ceramide deficiency may account, at least in part, for the dysfunction of the stratum corneum associated with ageing. Hence, treatments able to increase skin-ceramide levels could improve the epidermal barrier function in aged skin. Many animal testing and clinical trials are taken in that regard.
Highlights
The epidermis is a stratified epithelium consisting mainly of keratinocytes (Fig. 1)
An impaired epidermal barrier is associated with numerous skin diseases like atopic dermatitis, psoriasis or rare genodermatoses such as ichthyoses (Castiel-Higounenc et al, 2004; van Smeden et al, 2014)
In order to better understand the function of Patatin-like phospholipase domain containing 1 (PNPLA1) in the epidermis, we developed Pnpla1 knockout (KO) mice
Summary
The epidermis is a stratified epithelium consisting mainly of keratinocytes (Fig. 1) These cells differentiate throughout their migration from the basal layer towards the external surface of the skin. The stratum corneum is essential for the main function of the epidermis, the barrier function, vital for the organism It mainly fulfils the permeability barrier function by dampening transepidermal loss of water and electrolytes and by preventing entry of toxic or pathogenic agents. The stratum corneum and more the stratum corneum lipid structures are expected to undergo significant changes during the course of ageing. This has been little studied in comparison to other skin compartment like the dermis
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