Epidermal permeability barrier genes

The epidermal permeability barrier genes comprise a heterogeneous group of genes responsible for establishing and maintaining the skin's physical and chemical integrity, primarily within the stratum corneum [1, 5]. Key components include structural proteins like filaggrin (FLG), loricrin (LOR), and involucrin (IVL), which are essential for forming the cornified envelope, as well as enzymes like transglutaminase 1 (TGM1) and lipid transporters such as ABCA12 [5, 8]. These genes function collectively to prevent transepidermal water loss (TEWL) and provide a shield against environmental pathogens, allergens, and toxins [4, 9]. Mutations or downregulation of these genes are primary drivers in the pathogenesis of inflammatory skin diseases such as atopic dermatitis and psoriasis, as well as rare genetic disorders like ichthyosis [3, 13]. Therapeutic modulation of these genes is often achieved through the activation of nuclear receptors, such as the aryl hydrocarbon receptor (AhR) and peroxisome proliferator-activated receptors (PPARs), which upregulate the expression of barrier-associated proteins and promote lipid synthesis [1, 7]. Additionally, biological agents that block Th2 cytokines, such as dupilumab, help restore the expression of these barrier genes by alleviating the inflammatory suppression of keratinocyte differentiation [1, 13].

Other names

Skin barrier genesEpidermal differentiation complex genesCornified envelope genesSkin permeability barrier genes

Modulation of gene expression through nuclear receptors (e.g., AhR, PPAR, LXR) to upregulate structural proteins and lipid synthetic enzymes, or indirect restoration through cytokine inhibition to prevent the suppression of terminal differentiation markers [1, 3, 7].