Universiteit Leiden

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Research project

Human epidermal lipid biosynthesis in health and disease

How are the epidermal lipid pathways involved in health and disease.

Human epidermal skin (Figure 1A) acts as a permeability barrier that protects us from excessive water loss as well as unwanted infiltration of exogenous compounds in the deeper skin layers. This barrier is primarily located at the outermost skin layer, the stratum corneum (SC), and consists of dead skin cells (corneocytes) embedded in a matrix of lipids with a highly specific composition. SC lipids primarily consist of three different lipid classes: cholesterol, fatty acids, and ceramides. In healthy skin, SC-lipids hinder penetration of pathogens into the deeper layers of the skin (Figure 1B). However, when changes are observed in the lipid composition, the SC barrier may become impaired, which facilitates the penetration of pathogens and provoke an immune response. A well-known example is atopic eczema: an inflammatory skin disease characterized by red, dry, and itchy skin spots. Previous studies have demonstrated that the skin barrier in patients with atopic eczema is impaired, and that the degree of impairment depends on the changes in the lipids. However, the cause of these changes in lipid composition is still not understood. It is therefore of importance to study the lipid pathways that are involved in biosynthesis of the SC-lipids, and determine possible relationships between enzyme expression, enzyme activity, and the lipid profile in healthy and disease circumstances.

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