A human organotypic knock-down skin model to study molecules involved in epidermal keratinocyte differentiation. An alternative to knock-out animal experiments in dermatological research
Formation of the epidermal barrier is a complex process involving the tight regulation of the expression of structural proteins, enzymes and cytokines, implementing different signaling pathways depending on the differentiation stage of KC. Alterations of skin barrier formation occur as consequence of many skin diseases but can also be the primary event leading to skin diseases. Organotypic skin models have greatly contributed to delineate molecular mechanisms underlying the epidermal differentiation process. In this thesis we have adapted a human organotypic skin model to knock-down individual genes and study their impact on the differentiation of epidermal KC in vitro. Using this model we have provided new insights in the formation of the skin barrier of human skin.This work was partially supported by the European Union COST initiative on skin barrier in atopic dermatitis, by the Deutsche Forschungsgemeinschaft (SCHR 305 / 5-1) and by the Centre de Recherches et d´Investigations Èpidermiques et Sensorielles de CHANEL (CE.R.I.E.S). Financial support for printing of this thesis was provided by CellSystems.UBL - phd migration 201