Submitted on December 18, 2007
Accepted on May 13, 2008
MODULATION OF MOUSE INTESTINAL EPITHELIAL CELL TURNOVER IN THE ABSENCE OF ANGIOTENSIN CONVERTING ENZYME
Emir Q Haxhija1, Hua Yang1, Ariel U Spencer1, Hiroyuki Koga1, Xiaoyi Sun1, and Daniel H. Teitelbaum1*
1 Surgery, University of Michigan, Ann Arbor, Michigan, United States
* To whom correspondence should be addressed. E-mail: dttlbm{at}umich.edu.
Objective: Angiotensin converting enzyme (ACE) has been shown to be involved in regulation of apoptosis in non-intestinal tissues. This study examined the role of ACE in the modulation of intestinal adaptation utilizing ACE knockout mice (ACE-/-).
Methods: We utilized a 60% small bowel resection (SBR), as this model results in a significant increase in intestinal epithelial cell (EC) apoptosis as well as proliferation.
Results: Baseline villus height, crypt depth and intestinal EC proliferation were higher, and EC apoptosis rates were lower in ACE-/- compared to ACE+/+ mice. After SBR, EC apoptosis rates remained significantly lower in ACE-/- compared to ACE+/+ mice. Further, villus height and crypt depth after SBR continued to be higher in ACE-/- mice. The finding of a lower Bax to Bcl-2 protein ratio in ACE-/- mice may account for reduced EC apoptotic rates after SBR in ACE-/- compared to ACE+/+ mice. The baseline higher rate of EC proliferation in ACE-/- compared to ACE+/+ mice may be due to an increase in the expression of several EC growth factor receptors.
Conclusions: ACE appears to have an important role in the modulation of intestinal EC apoptosis and proliferation; and suggests that the presence of ACE in the intestinal epithelium has a critical role in guiding epithelial cell adaptive response.
