Role of mucins in inflammatory bowel disease: important lessons from experimental models.
Inflammatory bowel disease (IBD) is characterized by a chronically inflamed mucosa of the gastrointestinal tract, caused by an underlying immune imbalance and triggered by luminal substances, including bacteria. Mucus forms a gel layer covering the gastrointestinal tract, acting as a semi-permeable barrier between the lumen and the epithelium. Mucins, the building blocks of the mucus gel, determine the thickness and properties of mucus. In IBD in humans, alterations in both membrane-bound and secretory mucins have been described involving genetic mutations in mucin genes, changes in mucin mRNA and protein levels, degree of glycosylation, sulphation, and degradation of mucins. As mucins are strategically positioned between the vulnerable mucosa and the bacterial contents of the bowel, changes in mucin structure and/or quantity probably influence their protective functions and therefore constitute possible aetiological factors in the pathogenesis of IBD. This hypothesis, however, is difficult to prove in humans. Animal models for IBD permit detailed analysis of those aspects of mucins necessary for protection against disease. These models revealed pertinent data as for how changes in mucins, in particular in MUC2, imposed by immunological or microbial factors, may contribute to the development and/or perpetuation of chronic IBD, and shed some light on possible strategies to counteract disease.
Einerhand
Alexandra W C
AW
Laboratory of Paediatrics, Section Paediatric Gastroenterology and Nutrition, Room Ee 1571a, Erasmus Medical Centre and Sophia Children's Hospital, Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands. einerhand@kgk.fgg.eur.nl
Renes
Ingrid B
IB
Makkink
Mireille K
MK
van der Sluis
Maria
M
Büller
Hans A
HA
Dekker
Jan
J
D000818:Animals; D001419:Bacteria / Q000254:growth & development; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics / Q000382:microbiology / Q000503:physiopathology*; D007413:Intestinal Mucosa / Q000378:metabolism / Q000382:microbiology; D007422:Intestines / Q000382:microbiology; D009077:Mucins / Q000235:genetics / Q000502:physiology*
D009077:Mucins