Necrotizing enterocolitis (NEC) is a major cause of morbidity and mortality in premature infants; its etiology and pathogenesis remain elusive. NEC primarily affects premature infants suggesting that the immaturity of the mucosal barrier of the developing intestinal tract may be associated with the premature infant's particular susceptibility to mucosal injury. Trefoil factor family 3 (TFF3), a member of the newly defined trefoil factor family, is secreted abundantly at the mucosal surface by goblet cells throughout the small and large intestine in adults. As TFF3 has an important role in the maintenance and repair of the intestinal mucosal barrier, its deficiency in premature infants may play a role in the susceptibility of premature infants to NEC. This research proposal will characterize the developmental expression of TFF3 and examine the effect of prenatal steroids on its expression during rat intestinal development and injury. Specifically, rat intestinal tissues will be examined for TFF3 gene and protein expression at various developmental time points. Further, the effects of glucocorticoid on developmental expression of TFF3 will be determined. Using a rat NEC model, changes in TFF3 expression, as well as the effect of glucocorticoids on TFF3 expression and enteral TFF3 administration in prevention of NEC will be investigated. Further, TFF3 expression during human intestinal development will also be determined in two ways, first by examining TFF3 expression in intestinal tissues from early aborted fetuses and infants of different gestational age, and also by enzyme-linked immunoassay, to measure TFF3 in stool and compare TFF3 expression in stools of premature infants who develop NEC and of those without NEC. These studies should provide novel insights into the development of the intestinal mucosal barrier and unique possible strategies for the early diagnosis and prevention of NEC in premature infants.
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