Cell death by cornification

Eckhart, Leopold; Lippens, Saskia; Tschachler, Erwin; Declercq, Wim

doi:10.1016/j.bbamcr.2013.06.010

Cited by 515Skin and Cellular Biology ResearchCell death mechanisms and regulationGenetic and rare skin diseases.

Cell death by cornification

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Eckhart, Leopold, Lippens, Saskia, Tschachler, Erwin, Declercq, Wim·2013·Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

DOI 10.1016/j.bbamcr.2013.06.010

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Abstract

Epidermal keratinocytes undergo a unique form of terminal differentiation and programmed cell death known as cornification. Cornification leads to the formation of the outermost skin barrier, i.e. the cornified layer, as well as to the formation of hair and nails. Different genes are expressed in coordinated waves to provide the structural and regulatory components of cornification. Differentiation-associated keratin intermediate filaments form a complex scaffold accumulating in the cytoplasm and, upon removal of cell organelles, fill the entire cell interior mainly to provide mechanical strength. In addition, a defined set of proteins is cross-linked by transglutamination in the cell periphery to form the so-called cornified envelope. Extracellular modifications include degradation of the tight linkages between corneocytes by excreted proteases, which allows corneocyte shedding by desquamation, and stacking and modification of the excreted lipids that fill the intercellular spaces between corneocytes to provide a water-repellant barrier. In hard skin appendages such as hair and nails these tight intercorneocyte connections remain permanent. Various lines of evidence exist for a role of organelle disintegration, proteases, nucleases, and transglutaminases contributing to the actual cell death event. However, many mechanistic aspects of kearatinocyte death during cornification remain elusive. Importantly, it has recently become clear that keratinocytes activate anti-apoptotic and anti-necroptotic pathways to prevent premature cell death during terminal differentiation. This review gives an overview of the current concept of cornification as a mode of programmed cell death and the anti-cell death mechanisms in the epidermis that secure epidermal homeostasis. This article is part of a Special Section entitled: Cell Death Pathways.

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Exon 26A is rarely expressed and is detected under pathological conditions affecting keratinocyte differentiation, called parakeratosis, characterized by early cell death with retention of nuclear debris in corneocytes and an increase in keratin.
“Exon 26A, for example, is rarely expressed and is detected under pathological conditions that affect the process of keratinocyte differentiation, which is called parakeratosis and is characterized by early cell death with retention of nuclear debris in corneocytes and an increase in keratin [62].”
From Elastin structure and its involvement in skin photoageing (2017) · cites this paper as [62]
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Authors: Eckhart, L., Lippens, S., Tschachler, E., & Declercq, W.
Affiliations: Medical University of Vienna (AT)
Vlaams Instituut voor Biotechnologie (BE)
Corresponding author: Declercq, Wim
ORCID: Eckhart, Leopold
Lippens, Saskia
Tschachler, Erwin
Declercq, Wim
Venue: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
Publisher: Elsevier BV
Published: 2013-12
Volume: 1833
Issue: 12
Pages: 3471-3480
ISSN: 0167-4889 (ISSN-L)
DOI: 10.1016/j.bbamcr.2013.06.010
OpenAlex: W2031363300
Cited by: 515
References: 118
Citations by year: 2026: 18 · 2025: 34 · 2024: 60 · 2023: 47 · 2022: 40 · 2021: 54 · 2020: 45 · 2019: 46 · 2018: 40 · 2017: 36 · 2016: 39 · 2015: 35 · 2014: 20 · 2013: 1
FWCI: 3.65
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 365 d)
Locations: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research (publishedVersion)
PubMed (publishedVersion)
Ghent University Academic Bibliography (Ghent University) (submittedVersion)
Funders: VIB, Ghent University (BELSPO IAP 7/32)
Stichting tegen Kanker (2010-162)
FWO-Vlaanderen (G.0226.09N, 1.5.169.08, 1.5.058.12N)
Methusalem grant (BOF09/01M00709)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and rare skin diseases.
Keywords: keratinization, keratinocyte differentiation, programmed cell death, cornified envelope, keratin intermediate filaments, desquamation, skin barrier, anti-apoptotic pathways, epidermal homeostasis, corneocytes, proteolytic enzymes, nucleases
MeSH terms: Epidermal Cells, Filaggrin Proteins, Animals, Cell Differentiation, Humans, Models, Biological, Keratinocytes, Cell Death

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