Epidermal renewal and keratinisation

Also known as: keratinization, keratinisation, cornification, desquamation, epidermal turnover, skin renewal

The epidermis replaces itself roughly every four weeks as basal stem-cell progeny differentiate, keratinise and die to form the stratum corneum, which is then shed.

Overview

Basal → corneum transit≈2 weeks

Corneum transit≈2 weeks

Total renewal≈4 weeks (≈3–5 days in psoriasis)

Proliferation. Slowly cycling epidermal stem cells in the stratum basale (and in the hair-follicle bulge) produce transit-amplifying cells that divide a few times before committing to differentiation and detaching from the basement membrane.

Differentiation (keratinisation). In the stratum spinosum cells switch from K5/K14 to K1/K10 keratins, assemble thick keratin bundles anchored in desmosomes and begin forming lamellar bodies. In the stratum granulosum they accumulate keratohyalin granules (profilaggrin, loricrin) and discharge lamellar-body lipids into the intercellular space; tight junctions form. Cornification then occurs: lysosomal enzymes degrade the nucleus and organelles, profilaggrin is cleaved to filaggrin, which aggregates keratin filaments into dense macrofibrils, and transglutaminases cross-link involucrin, loricrin and other proteins into an insoluble cornified envelope to which ceramides are covalently bonded. This specialised programmed cell death differs from apoptosis.

Desquamation. In the outer corneum, serine proteases (kallikreins 5 and 7) digest corneodesmosomes so that single corneocytes are shed invisibly. Basal-to-granular transit takes ≈2 weeks and passage through the corneum another ≈2 weeks: total renewal ≈4 weeks (≈28 days) in young adults, lengthening with age. A rising calcium gradient, vitamin D, retinoids and growth factors (EGF, KGF) regulate the process.

Function

Continuous replacement of cells lost by wear

Generation of the stratum corneum barrier

Shedding of surface microbes and contaminants

Regulation

Epidermal calcium gradient; EGF/TGF-α, KGF (FGF7) from fibroblasts; vitamin D and retinoic acid nuclear receptors; Notch and p63 transcriptional programmes; inflammatory cytokines (IL-17, IL-22) in psoriasis.

Clinical significance

Psoriasis

IL-23/IL-17-driven hyperproliferation shortens epidermal transit to ≈3–5 days: keratinocytes reach the surface before completing cornification, leaving nuclei in the corneum (parakeratosis) and a thin or absent granular layer, with silvery scale.

Ichthyoses

Disorders of cornification causing fish-like scaling: ichthyosis vulgaris (filaggrin loss), X-linked ichthyosis (steroid sulfatase deficiency, impaired desquamation), lamellar ichthyosis (transglutaminase-1); harlequin ichthyosis (ABCA12) is severe.

Retinoids in dermatology

Vitamin A derivatives normalise keratinisation and reduce cohesion of corneocytes — used for acne, photoageing and psoriasis (acitretin); all oral retinoids are teratogenic.