Evidence for active Wnt signaling during postresection intestinal adaptation

Background: In the intestine, Wnt proteins are powerful regulators of cell proliferation, differentiation, and adhesion. Mutations of the adenomatous polyposis coli (APC) gene elevate nuclear β-catenin and provoke intestinal tumor formation. We sought to determine whether Wnt signaling is involved in adaptive response to massive small bowel resection (SBR). Methods: Male Min mice with a mutation of the APC gene and wild-type controls underwent a 50% proximal SBR or sham operation. After 3 days, villus height, crypt depth, and rates of proliferation and apoptosis were recorded in the remnant ileum. Results: After SBR, villus height and enterocyte proliferation were significantly greater in the Min mice. Western blotting demonstrated resection-induced increases in β-catenin, c-Myc, and E-cadherin after SBR, which was more pronounced in Min mice. Conclusions: Mutation of the APC gene and augmented Wnt signaling in the intestine results in an enhanced adaptive response to massive SBR. These data, for the first time, implicate an important role for Wnt signaling during the pathogenesis of resection-induced intestinal adaptation.