Cell death in the skin

  title={Cell death in the skin},
  author={Saskia Lippens and Esther Hoste and Peter Vandenabeele and Patrizia Agostinis and Wim Declercq},
The skin is the largest organ of the body and protects the organism against external physical, chemical and biological insults, such as wounding, ultraviolet radiation and micro-organisms. The epidermis is the upper part of the skin that is continuously renewed. The keratinocytes are the major cell type in the epidermis and undergo a specialized form of programmed cell death, called cornification, which is different from classical apoptosis. In keep with this view, several lines of evidence… 
Burn Injury: Mechanisms of Keratinocyte Cell Death
The underlying mechanisms of RCD and the skin’s responses to thermal stress may lead to improved strategies for treating cutaneous burn trauma and caspase-independent pathways have been suggested in regulated cell death.
Caspase-8 for Outer Harmony
Although differentiation in the outermost epidermal layers of these mice is normal, the mice suffer from strong cutaneous inflammation because of enhanced production and secretion of the proinflammatory cytokine pro-interleukin-1α.
Exposure to Carbon Ions Triggers Proinflammatory Signals and Changes in Homeostasis and Epidermal Tissue Organization to a Similar Extent as Photons
Cell and molecular changes related to the early inflammatory response of human skin irradiated with carbon ions are measured, in particular cell death induction and changes in differentiation and proliferation of epidermal cells during the first days after exposure.
Microenvironment‐dependent homeostasis and differentiation of epidermal basal undifferentiated keratinocytes and their clinical applications in skin repair
  • J. Nie, X. Fu, W. Han
  • Biology, Medicine
    Journal of the European Academy of Dermatology and Venereology : JEADV
  • 2013
Exploring the characteristics and regulation mechanisms of microenvironment‐dependent homeostasis and differentiation of epidermal basal undifferentiated keratinocytes is necessary to understand skin development and wound repair and to design novel therapeutic strategies for skin wound healing.
Immunohistochemical study of the apoptosis process in epidermal epithelial cells of rats under a physiological condition.
The results suggest that epidermal apoptosis is induced by the interaction between Fas and Fas-L and the activation of caspase-10, and might initially proceed through a mitochondrial-independent pathway, and that a mitochondria-dependent pathway finally accelerated under physiological conditions.
Plakoglobin-dependent regulation of keratinocyte apoptosis by Rnd3
A novel plakoglobin-dependent role for Rnd3 in the regulation of keratinocyte cell death is proposed, which is associated with resistance to cisplatin-mediated apoptosis in keratinocytes and this resistance is mediated through the desmosomal protein plakemia.
Protective Effects of Salicornia europaea on UVB-Induced Misoriented Cell Divisions in Skin Epithelium
The findings uncover a new mechanism by which S. europaea responds to the spindle misorientation induced by UVB, which preserves the axis of division of basal keratinocytes from UVB-induced perturbations.
Epidermal polarity genes in health and disease.
The importance of polarizing processes and their molecular regulators in epidermal morphogenesis and homeostasis is addressed and how alterations in polarity may contribute to skin disease is discussed.
Genetically Programmed Cell Death: Concepts of Death and Immortality in the Age of the Genome
This paper introduces this discussion and explores some of the implications of programmed cell death for a Christian understanding of the relationship between life and death.


Life and death signaling pathways contributing to skin cancer.
Four topics are explored: a review of the life and death signaling pathways operative in normal human skin that prevents premature apoptosis of KC with an emphasis on nuclear factor kappaB (NFkappaB) survival signals; the molecular pathways that are engaged and regulate apoptosis after normal KC are exposed to ultraviolet (UV) light; the apoptotic resistant mechanisms that premalignant and malignant KC utilize to avoid cell death; therapeutic strategies that can render malignant cells more susceptible to apoptosis.
Oxidative stress in the pathogenesis of skin disease.
One approach to preventing or treating these ROS-mediated disorders is based on the administration of various antioxidants in an effort to restore homeostasis.
Ultraviolet radiation-induced apoptosis in keratinocytes: on the role of cytosolic factors.
Death penalty for keratinocytes: apoptosis versus cornification
It is concluded that despite earlier confusion, apoptosis and cornification occur through distinct molecular pathways, and that possibly antiapoptotic mechanisms are implicated in the terminal differentiation of keratinocytes.
Gadd45a protects against UV irradiation-induced skin tumors, and promotes apoptosis and stress signaling via MAPK and p53.
It is demonstrated that Gadd45a is a critical factor protecting the epidermis against UV radiation-induced tumorigenesis by promoting damaged keratinocytes to undergo apoptosis and/or cell cycle arrest, two crucial events that prevent the expansion of mutant or deregulated cells.
The cornified envelope: a model of cell death in the skin
New insights into the molecular mechanisms and the physiological endpoints of cornification are increasing the understanding of the pathological defects of this unique form of programmed cell death, which is associated with barrier malfunctions and ichthyosis.
Epidermal differentiation: the role of proteases and their inhibitors.
  • P. Zeeuwen
  • Biology
    European journal of cell biology
  • 2004
Recent findings on the role of cystatin M/E and legumain as a functional dyad in skin and hair follicle cornification, a paradigm example of the regulatory functions exerted by epidermal proteases, will be discussed.
Apoptosis in keratinocytes is not dependent on induction of differentiation.
It is demonstrated that when cultured undifferentiated keratinocytes have their adhesive interactions interrupted by either enzymatic treatment and suspension in a semi-solid methyl cellulose medium, or exposure to antibodies against beta 1 integrins and E-cadherin, induction of differentiation occurs, as well as apoptosis.
Regulation of apoptosis by p53 in UV-irradiated human epidermis, psoriatic plaques and senescent keratinocytes
UV-light induces DNA damage in human epidermal KCs triggering p53 activation, and subsequent apoptosis involving distinct cell layers and kinetics, which depends not only on the location within various layers of epidermis and levels of p53, but may also involve p53activation via post-translational modifications.
NF-κB determines localization and features of cell death in epidermis
It is shown that NF-kappaB protects normal epithelial cells from apoptosis induced by both TNFalpha and Fas, whereas NF- kappaB blockade enhances susceptibility to death via both pathways, and indicates that, in stratified epithelium, such cell death normally proceeds via a distinct pathway that is resistant to NF-KappaB and its antiapoptotic target effector genes.