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 beta-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 beta-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.
Division of General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229-3039, USA.
Nicole P
NP
Bernal
Wolfgang
W
Stehr
Yufang
Y
Zhang
Sherri
S
Profitt
Christopher R
CR
Erwin
Brad W
BW
Warner
D000818:Animals; D017209:Apoptosis; D015820:Cadherins / Q000378:metabolism; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000378:metabolism; D066246:ErbB Receptors / Q000502:physiology*; D007082:Ileum / Q000166:cytology / Q000378:metabolism / Q000601:surgery*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D015398:Signal Transduction; D051155:Wnt1 Protein / Q000378:metabolism* / Q000502:physiology; D051176:beta Catenin / Q000378:metabolism
D015820:Cadherins; D016271:Proto-Oncogene Proteins c-myc; D051155:Wnt1 Protein; D051176:beta Catenin; D019938:Cyclin D1; D066246:ErbB Receptors