Bricks and mortar of the epidermal barrier
Open accessAbstract
A specialized tissue type, the keratinizing epithelium, protects terrestrial mammals from water loss and noxious physical, chemical and mechanical insults. This barrier between the body and the environment is constantly maintained by reproduction of inner living epidermal keratinocytes which undergo a process of terminal differentiation and then migrate to the surface as interlocking layers of dead stratum corneum cells. These cells provide the bulwark of mechanical and chemical protection, and together with their intercellular lipid surroundings, confer water-impermeability. Much of this barrier function is provided by the cornified cell envelope (CE), an extremely tough protein/lipid polymer structure formed just below the cytoplasmic membrane and subsequently resides on the exterior of the dead cornified cells. It consists of two parts: a protein envelope and a lipid envelope. The protein envelope is thought to contribute to the biomechanical properties of the CE as a result of cross-linking of specialized CE structural proteins by both disulfide bonds and N(epsilon)-(gamma-glutamyl)lysine isopeptide bonds formed by transglutaminases. Some of the structural proteins involved include involucrin, loricrin, small proline rich proteins, keratin intermediate filaments, elafin, cystatin A, and desmosomal proteins. The lipid envelope is located on the exterior of and covalently attached by ester bonds to the protein envelope and consists of a monomolecular layer of omega-hydroxyceramides. These not only serve of provide a Teflon-like coating to the cell, but also interdigitate with the intercellular lipid lamellae perhaps in a Velcro-like fashion. In fact the CE is a common feature of all stratified squamous epithelia, although its precise composition, structure and barrier function requirements vary widely between epithelia. Recent work has shown that a number of diseases which display defective epidermal barrier function, generically known as ichthyoses, are the result of genetic defects of the synthesis of either CE proteins, the transglutaminase 1 cross-linking enzyme, or defective metabolism of skin lipids.
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The stratum corneum consists of dead keratin-filled cells embedded in a lipid matrix, providing a tough insoluble layer that separates the outside from the inside.
“This layer consists of dead keratin-filled cells embedded in a lipid matrix, thus providing a tough insoluble layer that separates the outside from the inside (Nemes and Steinert, 1999).”
From E‐cadherin is essential for in vivo epidermal barrier function by regulating tight junctions (2005) · cites this paper as Nemes and Steinert, 1999
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- Authors
- Nemes, Z., & Steinert, P. M.
- Affiliations
- National Institutes of Health (US)
- Venue
- Experimental & Molecular Medicine
- Published
- 1999-03
- Volume
- 31
- Issue
- 1
- Pages
- 5-19
- ISSN
- 1226-3613 (ISSN-L)
- 2092-6413
- OpenAlex
- W1972549014
- Cited by
- 567
- References
- 177
- Citations by year
- 2026: 9 · 2025: 21 · 2024: 15 · 2023: 24 · 2022: 21 · 2021: 22 · 2020: 28 · 2019: 25 · 2018: 19 · 2017: 7 · 2016: 20 · 2015: 25 · 2014: 18 · 2013: 23 · 2012: 26
- FWCI
- 7.45
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Experimental & Molecular Medicine (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advancements in Transdermal Drug Delivery
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Keywords
- skin barrier, cornified envelope, stratum corneum, keratinocyte terminal differentiation, transglutaminase 1, involucrin, loricrin, intercellular lipids, water permeability, desmosomal proteins, keratin intermediate filaments, ichthyosis, skin barrier dysfunction
- MeSH terms
- Animals, Cell Membrane, Epidermis, Humans, Ichthyosis, Membrane Lipids, Membrane Proteins, Transglutaminases, Keratinocytes
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