p21 (WAF1/CIP1) is required for the mitogenic response to intestinal resection.
BACKGROUND
Increased enterocyte proliferation and apoptosis characterize the intestinal adaptive response to massive small bowel resection (SBR). Since p21 (WAF1/CIP1) has been implicated to play a role in cellular differentiation and apoptosis, this study tested the hypothesis that p21 is obligatory for adaptation to occur.


METHODS
p21-null (n = 36) and wild-type (C57B1/6, n = 19) mice underwent a 50% SBR or sham operation. After 3 days, parameters of adaptation (ileal wet weight, villus/crypt morphology, and ileal protein content), an enterocyte proliferation index (PI), and an apoptotic index (AI) were determined in the residual ileum. In a separate set of experiments, p21-null (n = 11) and control (n = 20) mice underwent the aforementioned operative procedures and the remnant intestine was subjected to a reverse transcription polymerase chain reaction for p27 (KIP1).


RESULTS
Both AI and PI increased after SBR in the wild-type mice. In the p21-null mice, SBR increased AI, but did not affect the PI. After SBR, adaptive parameters increased in the wild-type mice, but failed to increase in the p21-null mice. The absence of p21 caused a baseline increase in p27 mRNA, which did not change after SBR.


CONCLUSIONS
p21 appears to be required to increase enterocyte proliferation and to augment the other parameters of intestinal adaptation. In the absence of p21, the proliferative and apoptotic responses to SBR are uncoupled. These results suggest a differential mechanism for the regulation of enterocyte proliferation and apoptosis in the adapting intestine.
Stern
L E
LE
Division of Pediatric Surgery, Children's Hospital Medical Center, Cincinnati, OH 45229-3039, USA.
Falcone
R A
RA
Kemp
C J
CJ
Erwin
C R
CR
Warner
B W
BW
D000222:Adaptation, Physiological; D000818:Animals; D017209:Apoptosis; D002455:Cell Division; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000502:physiology*; D007421:Intestine, Small / Q000166:cytology* / Q000601:surgery*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000502:physiology; D009124:Muscle Proteins; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D008840:Microfilament Proteins; D009124:Muscle Proteins; C058992:Tagln protein, mouse; D016159:Tumor Suppressor Protein p53