Effects of lifestyle and environmental factors on intestinal epithelial cell morphogenesis

Intestinal epithelium, the innermost cell layer of the intestine is capable of taking up nutrients and fluid, and forming an otherwise impermeable layer. In order to do this, intestinal epithelial cells must have the capacity to organize themselves internally as well as in respect to neighbor cells; a tightly regulated process. In this process an epithelial cell creates membrane domains differing in function and protein composition, each in contact with different parts of the environment: polarityThese functions may be perturbed by different factors. For example, in the inflammatory bowel diseases, where the intestinal epithelium is more ‘leaky’ influenced by pro-inflammatory cytokines or cigarette smoking.As an intestine is home to a complex interplay of many different types of cells, it is hard to discern any direct effects on epithelium in for example animal models.To assess direct effects, we have isolated a specific component, the intestinal epithelium itself. Therefore, to assess permeability and polarity, we have utilized a cell model that approximates these aspect of intestinal epithelium.This model consists of intestinal epithelial cell self-organizing into an impermeable hollow sphere, in which cells position themselves as if the cavity is the intestinal lumen. For this thesis we assessed the direct effects of different factors known from epidemiologic and clinical studies, such as cigarette smoking and the presence of pro-inflammatory cytokines on the self-organization in this cell model. This furthered insights into (pathological) environmental-epithelial interplay