Active -Catenin Signaling in the Small Intestine of Humans During Infancy

BackgroundWnt--catenin signaling is essential for homeostasis of intestinal stem cells in mice and is thought to promote intestinal crypt fission.AimsThe aim of this study was to investigate Wnt--catenin signaling in intestinal crypts of human infants.MethodsDuodenal biopsies from nine infants (mean, range 0.9years, 0.3-2years) and 11 adults (mean, range 43years, 34-71years) were collected endoscopically. Active -catenin signaling was assessed by cytoplasmic and nuclear -catenin, nuclear c-Myc, and cytoplasmic Axin-2 expression in the base of crypts. Tissues were stained by an immunoperoxidase staining technique and quantified as pixel energy using cumulative signal analysis. Data were expressed as meanSD and significance assessed by Student's t test.ResultsCrypt fission was significantly higher in infants compared to adults (16 +/- 8.6% versus 0.7 +/- 0.6%, respectively, p<0.0001). Expression of cytoplasmic and nuclear -catenin was 1.8-fold (p<0.0001) and 2.9-fold (p<0.0001) higher in infants, respectively, while cytoplasmic Axin-2 was 3.1-fold (p<0.0001) increased in infants. c-Myc expression was not significantly different between infants and adults. Expression was absent in Paneth cells but present in the transit amplifying zone of crypts. Crypt base columnar cells, which were intercalated between Paneth cells, expressed c-Myc.Conclusions p id=Par5Wnt--catenin signaling was active in crypt base columnar cells (i.e., intestinal stem cells) in human infants. This signaling could promote crypt fission during infancy. Wnt--catenin signaling likely acts in concert with other pathways to promote postnatal growth.