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Keratinocyte terminal differentiation
The epidermis is a stratified epithelium consisting mainly of keratinocytes. These cells differentiate throughout their migration from the basal layer towards the external surface of the epidermis. They finally change into corneocytes by a genuine process of programmed cell death, the cornification. Stacking of the corneocytes forms the stratum corneum, the outermost layer of the epidermis. The stratum corneum is a biological barrier of extreme importance, because it separates our body from its external environment. It presents a great mechanical resistance, opposes water losses, prevents the penetration of exogenous molecules and pathogenic microorganisms, and adsorbs a part of solar ultraviolet radiations. It is also a barrier with a fascinating biochemical and structural complexity.
We continue the description of the molecular basis of cornification. Dozens of proteins potentially involved have been identified following the analysis of differentiated keratinocyte transcriptome and proteome. We chose to study some of them, for example the family of 'S100-fused type proteins’. In addition, granular keratinocytes contain tubulo-vesicular structures derived from the Golgi apparatus, and whose content is discharged into the intercellular spaces (lipids responsible for the sealing of the stratum corneum, antimicrobial peptides, structural proteins, but also proteases and protease inhibitors responsible for the control of desquamation). We characterize the mechanisms and the proteins involved in regulating their intracytoplasmic traffic and their secretion. This fundamental objective is completed by a research with a medical purpose: understanding the pathophysiological mechanisms of Atopic Dermatitis, a chronic inflammatory disease of the skin that affects 15-20% of children in industrialized countries and is characterized by defects in the structure / function of the stratum corneum
To achieve our goals which connect the lab bench to the bedside, we use complementary methodologies in a multidisciplinary approach. Our work which could eventually lead to the discovery of new therapeutic targets is conducted in collaboration with the Department of Dermatology of the Toulouse University Hospital and with the support of experimental platforms and several industrial partners. They fit into the themes of European networks our group belong to, the COST program 'SKINBAD' and the E2BRN network.