[Regulation of the epidermal permeability barrier by lipids and hyperproliferation].
The stratum corneum, the permeability barrier between the internal and external milieu, is composed of protein-enriched cells and lipid-enriched intercellular domains. Lipid synthesis is localized in the keratinocytes. The lamellar bodies located in the keratinocytes secrete lipids (sphingolipids, free fatty acids and cholesterol) into in the intercellular spaces of the stratum corneum. A disturbance of barrier function results in an increase in the synthesis of free fatty acids, non-saponified lipids and cholesterol in all nucleated layers of the epidermis. Cholesterol synthesis is regulated by the enzyme HMG-CoA reductase. After acute disturbance of barrier function by acetone treatment the increase in cholesterol synthesis occurs mainly in the lower epidermis (stratum basale/stratum spinosum), while after chronic disturbance by a diet deficient in essential fatty acids the increase shifts to the upper epidermis (stratum granulosum). After barrier disturbance not only lipid but also DNA synthesis is stimulated. Stimulation of DNA synthesis leading to epidermal hyperplasia may be a second mechanism by which the epidermis tries to correct defects in barrier function. Artificial barrier repair with latex occlusion prevents an increase in lipid and in DNA synthesis. Chronic barrier impairment by topical application of lovastatin, an inhibitor of cholesterol synthesis, or by a diet deficient in essential fatty acid also leads to an increase in lipid and DNA synthesis and to epidermal hyperplasia. Epidermal lipid and DNA synthesis in essential fatty acid deficiency is independent of prostaglandin E2, but depends on n-6-unsaturated fatty acids such as linoleic and columbinic acid.
Proksch
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Hautklinik, Christian-Albrechts-Universität Kiel.
D000818:Animals; D002455:Cell Division / Q000502:physiology*; D002463:Cell Membrane Permeability / Q000502:physiology*; D002784:Cholesterol / Q000096:biosynthesis; D004261:DNA Replication / Q000502:physiology; D005110:Extracellular Space / Q000502:physiology; D005228:Fatty Acids, Essential / Q000502:physiology; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000502:physiology; D015603:Keratinocytes / Q000502:physiology*; D008055:Lipids / Q000096:biosynthesis*; D051379:Mice; D012869:Skin Absorption / Q000502:physiology*; D012871:Skin Diseases / Q000503:physiopathology; D014870:Water Loss, Insensible / Q000502:physiology
D005228:Fatty Acids, Essential; D008055:Lipids; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases
Regulation der epidermalen Permeabilitätsbarriere durch Lipide und durch Hyperproliferation.