Mucins in the gastrointestinal tract in health and disease

Abstract

Mucins form part of the dynamic, interactive mucosal defensive system active at the mucosal surface of the gastrointestinal tract. They are carbohydrate rich glycoproteins with unique molecular structure and chemical properties. The family of mucin (MUC) genes has 13 members that can be divided into secreted and membrane-associated forms each with characteristic protein domains and tissue specific glycosylation. Biosynthetic pathways have been described for the secreted and membrane-associated mucins and their eventual degradation and turnover. Mucins are present at all mucosal surfaces throughout the body in typical combinations and relate to the demands of organ function. Patterns of MUC gene expression with gastrointestinal site specific glycosylation are clearly important but are not yet well defined. Mucin production during fetal development shows distinct patterns that may correlate in many cases with neoplastic expression in adult life. An increasing number of protective proteins have been identified that appear in the adherent mucus layer at the mucosal surface. These proteins are co-secreted with mucins in some cases, interact with mucins at a molecular level through peptide and carbohydrate sites or benefit from the viscoelastic, aqueous environment afforded by the mucus gel to effect their defensive roles. The mechanism of many of these interaction remains to be elucidated but is clearly part of an integrated innate and adaptive mucosal defensive system relying on the mucins as an integral component to provide a mucus gel. Recent improvements in the description of MUC gene expression and mature mucin synthesis in the healthy gastrointestinal tract has formed a basis for assessment of mucosal disease at sites throughout the tract. Pathological patterns of mucin expression in disease appear to follow tissue phenotype, so that gastric and intestinal types can be defined and appear in metaplasia in e.g. esophagus and stomach. Adaptation of previous mucin based, histochemical classification of intestinal metaplasia to assess MUC gene expression has proved helpful and promises greater value if reliably combined with mucin linked glycosylation markers. Few changes in MUC gene expression or polymorphism have been detected in inflammatory bowel diseases in contrast to malignant transformation. Glycosylation changes however, are evident in both types of disease and appear to be early events in disease pathogenesis. Review of the major mucosal diseases affecting the gastrointestinal tract in childhood reveals parallel patterns to those found in adult pathology, but with some novel conditions arising through the developmental stages at lactation and weaning. The impact of bacterial colonization and nutrition at these stages of life are important in the evaluation of mucosal responses in pediatric disease.

Muc-2–Deficient Mice Display a Sex-Specific, COX-2–Related Impairment of Gastric Mucosal Repair

“…[1][2][3][4] Mucins, the carbohydrate-rich glycoprotein building blocks of the mucus gel, determine both the thickness and the major properties of mucus. 6,7 There are 21 distinct mucin genes.…”

“…1 In the stomach, mucus helps to reduce bacterial colonization, aids in protecting the epithelium from damage induced by ingested substances, acid, and pepsin, and contributes significantly to repair of epithelial damage. [1][2][3][4] That last effect is attributable to the contribution of mucus in the formation of a microenvironment over sites of mucosal injury, which is conducive to restoration of epithelial integrity. 4 Disruption of mucus in that circumstance leads to progression of tissue injury to deeper layers of the mucosa, with significant bleeding.…”

Selective expression of gastric mucin MUC6 in colonic sessile serrated adenoma but not in hyperplastic polyp aids in morphological diagnosis of serrated polyps

“…On the other hand, MUC5AC and MUC6 are two gastric type mucins that are expressed in the surface foveolar epithelium and deep antral/pyloric glands, respectively. [17][18][19] Aberrant and bidirectional gastric differentiations of foveolar mucin (MUC5AC) and pyloric mucin (MUC6) have been reported in colonic serrated adenomas and hyperplastic polyps. 20 In that article, the authors indicated that MUC5AC-positive cells are typically located throughout the entire length of the crypts, whereas cells expressing MUC6 are present only in the basal crypts.…”

Transitional metaplasia in intestinal epithelium of rats submitted to intestinal cystoplasty and treatment with L -lysine

“…The characteristics and functions of this barrier have been the object of much research as Transitional metaplasia in intestinal epithelium of rats submitted to intestinal cystoplasty and treatment with L-lysine Santos AM et al changes in barrier composition are known to be associated with severe gastrointestinal problems (inflammatory bowel disorders) 22,23 , urinary diversions with intestinal segments 24 , Barrett's esophagus and colorectal cancer 22,23 . Some changes in MUC gene expression or polymorphism have been detected in inflammatory bowel disorders, but not in malignant transformation 23 .…”