From secretion to desquamation: The pathway between stratum granulosum and stratum corneum keratinocytes.

Scriptie/masterproef: Doctoral Thesis


The skin barrier research has been initiated in our
department 10 years ago. The continuous search
for keys of evidence that permits to link
epidermal biology to epidermal structure and
function has been the goal of our research group
ever since. The barrier function of the skin
resides in the stratum corneum, formed by the
secretion of lamellar bodies (LB) and the terminal
differentiation of stratum granulosum (SG)
keratinocytes. This work brings new insights to
explain the pathophysiological mechanisms
involved in the formation of the epidermal
barrier. More specifically we investigated the role
of 1) serine protease (SP)/protease-activated
receptor-2 (PAR-2) signaling, 2) lipid
rafts/caveolae and caveolin-1, and 3) the actin
cytoskeleton. Acute barrier abrogation
accelerates the secretion of intercellular lipids
and the formation of new corneocytes. We found
that PAR-2 is responsible for the activation of the
kinase cascade inducing F/G-actin rearrangements
and cytoskeletal remodeling,
resulting in the arrest of LB secretion and the
induction of the transition of SG cells into
corneocytes. In parallel, the secretion of LB in
the cytosol of the SG cells is initiated, allowing
the insertion of caveolin-1 into the apical plasma
membrane and caveolae formation. This
phenomenon that occurs following barrier
abrogation is important to serve as a "brake" in
LB secretion, the induction of terminal
differentiation and the arrest of proliferation.
These findings have potential clinical and
therapeutic implications in several skin disorders
characterized by deficient LB secretion and
abnormal differentiation.
Datum Prijs29 okt 2010
Toekennende instantie
  • Vrije Universiteit Brussel
BegeleiderJean-Pierre Hachem (Promotor), Diane Roseeuw (Promotor), Kris Thielemans (Jury), Kristien De Paepe (Jury), Brigitte Velkeniers-Hoebanckx (Jury), Miriam Marichal (Jury), Matthias Schmuth (Jury), Yves Poumay (Jury) & M. Garmyn (Jury)

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