TREFOIL PEPTIDES ARE EARLY MARKERS OF GASTROINTESTINAL MATURATION IN THE RAT

Trefoil peptides are members of a unique family of proteins found pred ominately throughout the gastrointestinal tract, whose proposed functi ons include mucus stabilization, stimulation and/or differentiation of epithelial cells during wound repair. Recent trefoil knockout studies have reported delays in epithelial cell migration or maturation pathw ays together with almost a complete lack of mucus. In order to fully e xplore the role of trefoil peptides in gastrointestinal maturation, th ese studies were undertaken to accurately characterize the expression of trefoil peptides in the developing rat gut. The results of RPA sugg est that trefoil mRNA's are expressed as early as 15 days post coitus (dpc) in the intestine and stomach, Proteins are detected at 17 dpc by radioimmunoassay and immunohistochemical studies, which localize tref oil peptide expression to the lumenal surface of epithelial cells. At 17 dpc the gut is lined by pseudo-stratified, undifferentiated epithel ial cells. Polarized, columnar cells are not detected until at least 1 8 dpc, with sparse mucus staining and parietal cell markers not being detected until 18 and 19 dpc respectively. This data demonstrates that trefoil peptides are early markers of epithelial cell maturation in t he developing rat gut. The time course of their expression, well befor e the mucus cell type is specified, suggests a potential role in epith elial cell differentiation.