Of Mice and Mucins: Models for studying the role of mucins in the intestine
The small intestine is the major organ for the absorption of nutrients and also secretes enzymes to complete the digestive processes started in the stomach1-5. A 30- 50% loss (remaining length, <75 cm in children and <200 cm in adults) often leads to malabsorption, with resultant severe diarrhea, dehydration, electrolyte imbalances, nutrient deficiencies and weight loss6, 7. The small intestine from proximal to distal is divided into the duodenum, jejunum, and ileum. The lining of the small intestine is a single-layered epithelium. It covers the surface area of the villi that project into the lumen, and lines the crypts that descend into the underlying connective tissue. Dividing stem cells lie protected in the depth of the crypts. These stem cells generate four types of differentiated progeny: (i) enterocytes, with densely packed microvilli on their surfaces to increase their active area, are absorptive in function2; (ii) goblet cells, secreting the mucin Muc28-11 and peptides such as trefoil factor 3 (Tff3)12, both products which serve protective roles in the gut; (iii) Paneth cells, involved in the innate defense system by secreting cryptdins, proteins of the defensin family that kill bacteria13-15, and (iv) enteroendocrine cells, producing peptide hormones that act on neurons and other cell types in the gut wall and regulate growth, proliferation and digestive activities of cells of the gut and other tissues2, 6, 16. All of these cells stem from undifferentiated multipotent stem cells located near the bottoms of the crypts, above the Paneth cells (Fig. 1A). These multipotent stem cells cannot be conclusively identified as they can produce all cell types within the epithelium. The regulatory mechanism behind lineage specification has not yet been fully elucidated as it is complex and specific markers are lacking17. The large intestine, or colon, joins the small intestine at the ileum via a T-shaped junction.
|Publisher||Erasmus MC: University Medical Center Rotterdam|
|Promotor||Büller, H.A. (Hans)|
|Sponsor||Sophia Foundation for Scientific Research, Netherlands Organization of Scientific Research, The Foundation “De Drie Lichten” (Leiden), Inserm (Paris), Association François Aupetit (Paris), Netherlands Society of Gastroenterology, J.E. Jurriaanse Stichting, Nestlé Nederland B.V., AstraZeneca BV, Nutricia Nederland BV, Numico Research, Tramedico, Zambon Nederland B.V., BD Biosciences.|
van der Sluis, M.. (2006, November 29). Of Mice and Mucins: Models for studying the role of mucins in the intestine. Erasmus MC: University Medical Center Rotterdam. Retrieved from http://hdl.handle.net/1765/17413