p21 (WAF1/CIP1) is required for the mitogenic response to intestinal resection

Background. Increased enterocyte proliferation and apoptosis characterize t he intestinal adaptive response to massive small bowel resection (SBR), Sin ce p21 (WAF1/CIP1) has been implicated to play a role in cellular different iation and apoptosis, this study tested the hypothesis that p21 is obligato ry for adaptation to occur, Materials and methods. p21-null (n = 36) and wild-type (C57B1/6, n = 19) mi ce underwent a 50% SBR or sham operation. After 3 days, parameters of adapt ation (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-nu ll (n = 11) and control (n = 20) mice underwent the aforementioned operativ e procedures and the remnant intestine was subjected to a reverse transcrip tion polymerase chain reaction for p27 (KIP1). Results. Both AI and PI increased after SBR in the wild-type mice. In the p al-null mice, SBR increased AI, but did not affect the PI. After SBR, adapt ive parameters increased in the wild-type mice, but failed to increase in t he p21-null mice. The absence of p21 caused a baseline increase in p27 mRNA , which did not change after SBR, Conclusion. p21 appears to be required to increase enterocyte proliferation and to augment the other parameters of intestinal adaptation. In the absen ce of p21, the proliferative and apoptotic responses to SBR are uncoupled. These results suggest a differential mechanism for the regulation of entero cyte proliferation and apoptosis in the adapting intestine. (C) 2000 Academ ic Press.