The intestinal epithelium during damage and regeneration : cell type-specific responses in experimental colitis and after cytostatic drug treatment

In the first part of this thesis the role of the colonic epithelium and in particular its associated mucus-layer during IBD and in several experimental colitis models is discussed (Chapter 2). In Chapter 3-5 our investigations regarding the colonic epithelium in rat during the different phases ofDSS-induced acute colitis are described. Studied are: A. clinical symptoms, morphology, proliferation and apoptosis (Chapter 3). B. enterocyte-specific gene expression, goblet cell-specific gene expression, and the Muc2 - and TFF3 secretion capacity of goblet cells, as a measure of enterocyte and goblet cell functioning (Chapters 4 and 5). C. goblet cell-specific Muc2 biosynthesis, Muc2 sulfation, and Muc2 secretion (Chapter 5). These parameters were studied in conjunction during the onset of disease, active disease and the regenerative phase of DSS-induced colitis, in the proximal and distal colon to obtain insight in the specific colonic functions during damage and regeneration In the second part of this thesis the small intestinal epithelium after treatment with the cytostatic drug MTX is investigated. Described are: A. clinical symptoms, morphology, proliferation, apoptosis, and enterocyte-, goblet cell-, and Paneth cell specific gene expression in the 'normal' small intestinal epithelium, i.e. the epithelium distant from the Peyer's Patches (Chapter 6). B. the above described parameters in the PP-associated epithelium, and compared these with alterations seen in the small intestinal located more distantly from PP (Chapter 7). These parameters were studied on various days after MTX-treatment in the duodenum, jejunum, ileum, and colon to obtain a complete picture of the epithelial functions during MTX-induced damage and regeneration. Finally, by comparing the DSS-induced colonic damage with the MTX-induced small intestinal damage, the obtained insight in the types of damage and damage control in the colon and small intestine are discussed (Chapter 8).

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