Modulation of mouse intestinal epithelial cell turnover in the absence of angiotensin converting enzyme.
Angiotensin converting enzyme (ACE) has been shown to be involved in regulation of apoptosis in nonintestinal tissues. This study examined the role of ACE in the modulation of intestinal adaptation utilizing ACE knockout mice (ACE-/-). A 60% small bowel resection (SBR) was used, since this model results in a significant increase in intestinal epithelial cell (EC) apoptosis as well as proliferation. Baseline villus height, crypt depth, and intestinal EC proliferation were higher, and EC apoptosis rates were lower in ACE-/- compared with ACE+/+ mice. After SBR, EC apoptosis rates remained significantly lower in ACE-/- compared with ACE+/+ mice. Furthermore, 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 with ACE+/+ mice. The baseline higher rate of EC proliferation in ACE-/- compared with ACE+/+ mice may be due to an increase in the expression of several EC growth factor receptors. In conclusion, 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.
Haxhija
Emir Q
EQ
Section of Pediatric Surgery, Department of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA.
Yang
Hua
H
Spencer
Ariel U
AU
Koga
Hiroyuki
H
Sun
Xiaoyi
X
Teitelbaum
Daniel H
DH
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000166:cytology*; D005786:Gene Expression Regulation; D007082:Ileum / Q000166:cytology / Q000201:enzymology; D007413:Intestinal Mucosa / Q000166:cytology* / Q000201:enzymology; D007583:Jejunum / Q000166:cytology / Q000201:enzymology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D007703:Peptidyl-Dipeptidase A / Q000235:genetics* / Q000378:metabolism
D007703:Peptidyl-Dipeptidase A