Despite progress in regenerative medicine, with age,
the skin loses its properties in an irreversible
manner. The ATIP-Avenir team “Epidermal homeostasis
and tumorigenesis” directed by Chloé Féral, an
Inserm researcher at the French Cancer and Aging
Research Institute (Inserm/CNRS/Université Sophia
Antipolis), has just defined the cellular and
molecular mechanisms involved in maintaining skin
cells and skin healing in advanced years. These
mechanisms, described in vivo in mice, engage
molecule CD98hc, which is involved in epidermis
renewal and could be an indicator of the skin’s
capacity for regeneration.
Skin renewal is driven by stem keratinocytes. The
latter have two properties: active division and
differentiation. Each keratinocyte produces two
identical daughter cells. One remains static and
divides again, whereas the other migrates to the
upper layer, the differentiation layer, where it
will provide the different types of skin cellls. ©
I-STEM
The epidermis, the surface layer of the skin, is
mainly composed of keratinocytes cells, which, in
humans, are renewed continuously over a 21-day cycle.
These cells are located on a membrane made up of
components from the extracellular matrix that
provides the junction with the dermis, the deep
layer of the skin (see diagram).
The epidermis is renewed by cell proliferation and
differentiation that maintains the balance of adult
tissues. This balance, known as “homeostasis”, is
essential for tissues to function correctly and any
alterations to it are responsible for the physical
changes associated with aging: sagging skin due to
reduced skin cell proliferation, wound healing
defects, loss of hair, etc.
The ATIP-Avenir team “Epidermal homeostasis and
tumorigenesis” directed by Inserm researcher Chloé
Féral, studied the numerous cellular factors
involved in maintaining this balance. Particular
attention was paid to CD98hc, a molecule known for
its interaction with receptors that cause skin aging.
With age, the activity of the transporter CD98hc and
integrins (the receptors connected to the components
in the extra cellular matrix) is disturbed. However,
until now the mechanisms involved had never been
identified.
Through their work, the researchers showed in vivo
in mice that removing the gene CD98hc (coding gene
for transporter CD98hc) disturbs skin balance and
the healing process. By modifying cell proliferation
and migration, removing this gene also causes a
fault in the hair follicle cycle. The researchers
have deciphered all the complex mechanisms
associated with CD98hc, particularly integrin
deregulation caused by this missing molecule in
vivo. They confirm what was described in vitro: the
amino acid transporter CD98hc modules the integrin
signal, which is essential for skin renewal. As such,
CD98hc actively participates in skin renewal through
the efficient and widespread recruitment of skin
cells when needed (healing a wound, for example).
“CD98hc appears to be necessary for rapid and
effective skin renewal. Its reduced expression,
observed in vivo in elderly mice, confirms its role
in maintaining tissues, the hair follicle cycle and
healing, which are disturbed with age,” states Chloé
Féral. “The status of carrier CD98hc in vivo could
be an indicator of the skin’s capacity to renew
itself” she concludes.
For more information
The results were published in the Journal of
Experimental Medicine review (http://www.ncbi.nlm.nih.gov/pubmed/23296466)
http://english.inserm.fr/
(MDN)
|