Mucus, epithelial mucins and cytoprotection

Mucus, epithelial mucins and cytoprotection Epithelial mucins are widely accepted to play cytoprotective roles in the gastrointestinal tract. However, the number and nature of these complex glycoproteins is only just beginning to emerge. We aimed to identify the mucins in biopsies from human small intestine and colon in health and disease, by raising specific antisera and studying the biosynthesis of the individual mucins and by studying the mucin mRNA levels. A simple working hypothesis would be that certain mucins form a mucus layer and that this mucus layer forms a selective barrier between the lumen of the organ and the vulnerable epithelium. This hypothesis is based on several observations [ 1,2]. (1) Mucus layers are found in each of the hollow organs in close contact with the outer world, such as airway, gastrointestinal and urogenital tracts. (2) The mucus layers are copious and are primarily composed of secretory mucins. (3) In vitro mucus layers with similar physicochemical properties to natural layers can be reconstituted from purified secretory mucins. (4) Proteolysis or reduction of the mucins destroys the gel-forming ability. (5) The thickness of the mucus layer seems to depend on the conditions within the luminal milieu, e.g. in the stomach and colon the harsh conditions necessitate a thick mucus layer, while such a layer is largely absent in the milder conditions within the small intestine. (6) Mucus secretion can be dramatically increased in response to acute threats to the epithelium. (7) In many chronic pathological situations, such as gastric ulcers or ulcerative colitis (UC), mucus depletion seems to be associated with the severity of the disease. Notwithstanding the compiled circumstantial evidence, the ‘cytoprotection hypothesis’ is difficult to test directly. This requires the measurement of a direct effect on the integrity of epithelial cells specifically because of the depletion of mucus. The most elegant approach would be to interfere specifically with the biosynthesis of a particular mucin and concomitantly to assess