Intestinal adaptation and enterocyte apoptosis following small bowel resection is p53 independent.
Adaptation following small bowel resection (SBR) signals enterocyte proliferation and apoptosis. Because p53-induced p21(waf1/cip1) may be important for apoptosis in many cells, we hypothesized that these genes are required for increased enterocyte apoptosis during adaptation. Male C57BL/6 (wild-type) or p53-null mice underwent 50% proximal SBR or sham operation (bowel transection-reanastomosis). Adaptation (DNA-protein content, villus height-crypt depth, enterocyte proliferation), appearance of apoptotic bodies, and p53 and p21(waf1/cip1) protein expression were measured in the ileum after 5 days. Adaptation was equivalent after SBR in both wild-type and p53-null mice as monitored by significantly increased ileal DNA-protein content, villus height, and enterocyte proliferation. The number of crypt apoptotic bodies increased significantly after SBR evenly in both wild-type and p53-null mice. In the p53-null mice, SBR substantially induced the expression of p21(waf1/cip1) protein in villus enterocytes. The p53-independent induction of p21(waf1/cip1) may account for the similar intestinal response to SBR between wild-type and p53-null mice. Intestinal adaptation and increased enterocyte apoptosis following intestinal resection occur via a p53-independent mechanism.
Shin
C E
CE
Division of Pediatric Surgery, Children's Hospital Medical Center, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229-3039, USA.
Falcone
R A
RA
Kemp
C J
CJ
Erwin
C R
CR
Litvak
D A
DA
Evers
B M
BM
Warner
B W
BW
D000222:Adaptation, Physiological; D000818:Animals; D017209:Apoptosis; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D020895:Enterocytes / Q000502:physiology*; D007421:Intestine, Small / Q000601:surgery*; D007422:Intestines / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics; D011184:Postoperative Period; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology*
C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016159:Tumor Suppressor Protein p53