Bcl-w deficiency perturbs enterocyte apoptosis and proliferation

Abstract

Background: After massive small bowel resection (SBR), increased rates of enterocyte apoptosis have been observed in the remnant bowel via regulation of specific bcl-2 family members. This study tested the hypothesis that adaptive mucosal growth could be attenuated by the absence of the anti-apoptotic factor bcl-w. Methods: Bcl-w-null and corresponding wild-type littermate (WT) mice underwent 50% proximal SBR or sham operation (bowel transaction/reanastomosis) and then sacrificed three days after operation. Adaptation was measured in the remnant ileum as alterations in wet weight, villus height, crypt depth, rates of enterocyte proliferation (% crypt cells stained for Ki67) and apoptosis (# apoptotic bodies/crypt). Results: Survival after SBR was 12/20 (60%) for bcl-w-null versus 14/21 (67%) for WT mice. Both groups of mice demonstrated significantly increased wet weight and crypt depth following SBR. On the other hand, villus height and proliferative index were attenuated in the bcl-w-null mice after SBR. In addition, although the expected increase in apoptosis after SBR was observed in the WT mice, bcl-w-null mice had higher baseline rates of apoptosis which did not significantly change in response to SBR (Figure). Conclusion: Bcl-w deficiency results in a baseline increase in enterocyte apoptosis and attenuation of the proliferative adaptation response to massive SBR. These data endorse an important role for bcl-w as a key regulator of enterocyte apoptosis and proliferation in the remnant bowel following massive intestinal loss.