Keratinization, barrier development and DE junction = Keratinization, barrier development and DE junction

다국어 초록 (Multilingual Abstract)

The epidermis is composed of stratified cell layers, which undergo programmed differentiation to allow for constant renewal of the skin. Epidermal stem cells, which account for 1 to 10% of basal layer cells, give rise to transit-amplifying cells which yield terminally differentiated cells. Epidermal proliferative unit (EPU), 2 mm in size, is a functionally independent packet of self-renewing interfollicular epidermis, and one stem cell resides at the base of each EPU. Normal transit time from basal layer to desquamation is 28 days. Keratins, the cytoskeleton of keratinocytes, belong to intermediate filaments; mature keratin filaments contain types I & II keratins in a 1:1 molar ratio. Keratinocytes produce K5/K14 (K15) in the basal layer, K1/K10 in suprabasal layers, K2 in granular layer, and K9, K6a/b, K16, K17 in palmoplantar skin. Besides structural support, keratins are involved in cell and tissue growth, skin pigmentation, keratinocyte migration and immunomodulation. At plasma membrane, keratins are linked by adapter proteins to 2 types of anchoring junctions, desmosomes between adjacent cells, and hemidesmosomes between cell and dermal matrix. Adapter proteins in desmosomes include desmogleins, desmocollins, plakoglobin and plakophilin, and in hemidesmosomes, BPAG1, BPAG2, plectin, α6β4 integrin and laminin-332/laminin-311. In DE junction, anchoring fibrils consisting of type VII collagen is the strongest tie between epidermis and dermis, followed by hemidesmosome. Skin barrier is formed by corneocytes (“bricks”) reinforced by cornified envelope (CE), and intercellular lipids (“mortar”). CE is a covalently cross-linked protein polymer that forms underneath, and eventually replaces, keratinocyte membrane in the granular layer. The isopeptide bonds of CE are catalyzed by transglutaminases, a group of calcium-dependent enzymes. Among protein constituents of CE, involucrin synthesis begins in spinous layer; loricrin is the major structural component of CE; and filaggrin aggregates keratins into bundles and is eventually degraded to free amino acids, yielding natural moisturizing factors (NMF). Lamellar bodies, containing glycosylceramides, sphingomyelin, phospholipids, serine proteases, antimicrobial peptides and hydrolytic enzymes, are extruded to interface at SG/SC interface and form lipid bilayers in SC. Polar lipid precursors are “processed” into non-polar lipids (ceramides [45%], cholesterol [25%], free fatty acids [15%]) by specific hydrolytic enzymes and form the “mortar” of SC. Epidermal kallikreins are serine proteases that degrade corneodesmosomes and thus play a key role in desquamation. Tight junctions, located in SG2 layer, are second line barrier, and gap junctions formed by connexins are intercellular gatekeepers. Barrier insults stimulate not only repair responses, but also initiate cytokine cascade; IL-1, TNF and IL-6 are stimulators of lipid synthesis. Epidermal differentiation and lamellar body secretion is coordinately regulated by calcium and nuclear hormone receptors.