Mucins in the gastrointestinal tract in health and disease

Mucins form part of the dynamic, interactive mucosal defensive system activ e at the mucosal surface of the gastrointestinal tract. They are carbohydra te rich glycoproteins with unique molecular structure and chemical properti es. The family of mucin (MUC) genes has 13 members that can be divided into secreted and membrane-associated forms each with characteristic protein do mains and tissue specific glycosylation. Biosynthetic pathways have been de scribed for the secreted and membrane-associated mucins and their eventual degradation and turnover. Mucins are present at all mucosal surfaces throug hout the body in typical combinations and relate to the demands of organ fu nction. Patterns of MUC gene expression with gastrointestinal site specific glycosylation are clearly important but are not yet well defined. Mucin pr oduction during fetal development shows distinct patterns that may correlat e in many cases with neoplastic expression in adult life. An increasing number of protective proteins have been identified that appea r 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 le vel through peptide and carbohydrate sites or benefit from the viscoelastic , aqueous environment afforded by the mucus gel to effect their defensive r oles. The mechanism of many of these interaction remains to be elucidated b ut is clearly part of an integrated innate and adaptive mucosal defensive s ystem relying on the mucins as an integral component to provide a mucus gel . Recent improvements in the description of MUC gene expression and mature mu cin synthesis in the healthy gastrointestinal tract has formed a basis for assessment of mucosal disease at sites throughout the tract. Pathological p atterns of mucin expression in disease appear to follow tissue phenotype, s o that gastric and intestinal types can be defined and appear in metaplasia in e.g. esophagus and stomach. Adaptation of previous mucin based, histoch emical classification of intestinal metaplasia to assess MUC gene expressio n has proved helpful and promises greater value if reliably combined with m ucin linked glycosylation markers. Few changes in MUC gene expression or po lymorphism have been detected in inflammatory bowel diseases in contrast to malignant transformation. Glycosylation changes however, are evident in bo th types of disease and appear to be early events in disease pathogenesis. Review of the major mucosal diseases affecting the gastrointestinal tract i n childhood reveals parallel patterns to those found in adult pathology, bu t with some novel conditions arising through the developmental stages at la ctation and weaning. The impact of bacterial colonization and nutrition at these stages of life are important in the evaluation of mucosal responses i n pediatric disease.