On the Role of the Epidermal Differentiation Complex in Ichthyosis Vulgaris, Atopic Dermatitis and Psoriasis

S. Hoffjan; S. Stemmler

Disclosures

The British Journal of Dermatology. 2007;157(3):441-449. 

In This Article

Epidermal Proliferation And Differentiation

Epidermal differentiation is a complex mechanism by which keratinocytes develop from a proliferative cell type in the basal cell layer of the epidermis into flattened, dead cells in the outermost layer, the so-called cornified layer or stratum corneum[3] (Fig. 1). During the various stages of this terminal differentiation, different proteins are expressed by epidermal cells. Proliferating keratinocytes in the basal layer predominantly express keratins K5 and K14. Under complex transcriptional control involving various cell-signalling pathways, most keratinocytes lose their ability to proliferate and adhere to the basal layer and subsequently enter the process of terminal differentiation.[4,5] Following the intermediate spinous layer, cells in the granular layer begin to express proteins required for cornification, for example, K1 and K10 keratin filaments. Additionally, the cells acquire keratohyaline granules that predominantly contain profilaggrin, the 400-kDa precursor protein of filaggrin. Profilaggrin is cleaved into ∼37-kDa filaggrin peptides that aggregate the keratin filaments into tight bundles, leading to a collapse of the cells into flattened squames.[3] Additional structural proteins, including loricrin, involucrin, trichohyalin and small proline-rich proteins (SPRRs), are expressed at this stage. Subsequently, the epidermal proteins are cross-linked by transglutaminases, establishing the so-called cornified envelope, a thick peripheral protein envelope that stabilizes each corneocyte.[6] Finally, lipids (e.g. ceramides) are synthesized in lamellar granules that are extruded into the extracellular space, building the so-called lipid envelope that further reinforces the epidermal barrier.[7]

In healthy individuals, there is a precise balance between proliferation of basal cells and desquamation of the cornified layer, while several skin diseases are characterized by imbalances in this complex mechanism.

Figure 1.

Epidermal differentiation and establishment of the cornified envelope. For terminal differentiation, epidermal cells move from the basallayer through the spinous layer and the granular layer towards the stratum corneum. During this process, they develop from mitotically activecells into dead, flattened squames. At the various stages of this development, different proteins are expressed (shown on the right side). Crosslinkingof epidermal proteins eventually leads to the establishment of the cornified envelope, a thick peripheral protein envelope that stabilizeseach corneocyte. Additionally, lipids are synthesized in lamellar granules which are subsequently extruded into the extracellular space where theysurround the corneocytes and build the lipid envelope. SPRRs, small proline-rich proteins.

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