Abstract
Necrotizing Enterocolitis (NEC) is a devastating disease of preterm infants. Immature intestinal barrier function has been implicated in its pathogenesis. Tight junctions (TJ), comprised of transmembrane Claudins which seal the paracellular space, are a vital component of the intestinal barrier and its regulation of intestinal permeability. However, little is known about how TJ development in the immature intestine influences changes in intestinal permeability. We screened mRNA expression of 29 TJ proteins by qRT‐PCR in the ileum of developing mice over the first 8 weeks of life. Selective TJ proteins were further analyzed by immunoblot analysis and localized by immunofluorescence labeling/confocal microscopy (IF). Temporal changes in expression were correlated with FITC‐dextran intestinal permeability assays. Most TJ proteins demonstrated decreased expression over time. However, Claudin‐3 and Claudin‐7 expression peaked at 3 weeks. IF demonstrated appropriate localization of Claudins in TJ after 3 weeks. Over the same period, intestinal permeability decreased. Changes in Claudin expression likely drive changes in intestinal permeability by tightening the paracellular space. Further studies are needed to elucidate what factors influence temporal changes in TJ expression and intestinal permeability and how they may affect predisposition to NEC.
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