TY - JOUR
T1 - Bax deficiency rescues resection-induced enterocyte apoptosis in mice with perturbed EGF receptor function
AU - Jarboe, Marcus D.
AU - Juno, Russell J.
AU - Bernal, Nicole P.
AU - Knott, Andrew W.
AU - Zhang, Yufang
AU - Erwin, Christopher R.
AU - Warner, Brad W.
N1 - Funding Information:
Supported by National Institutes of Health ROIDK59288 (BWW); and National Institutes of Health T32 GM 08478 (AWK and RJJ).
PY - 2004/8
Y1 - 2004/8
N2 - Background Adaptation after massive smallbowel resection (SBR) is associated with increased cell turnover, increased rates of enterocyte proliferation, and apoptosis. Epidermal growth factor receptor (EGFR) inhibition attenuates adaptation and increases apoptosis. Intestinal levels of bax appear to correlate with EGFR signaling. This study tested the hypothesis that bax is required for the exaggerated postresection apoptosis induced by perturbed EGFR signaling. Methods Waved-2 mice with impaired EGFR signaling were crossbred with bax-null mice. Offspring were subjected to either 50% proximal SBR or sham operation (bowel transection and reanastomosis). After 7 days, parameters of adaptation (villus height, wet weight), proliferation (% Ki-67 immunostaining of crypt cells), and apoptosis (# apoptotic bodies per crypt) were recorded in the remnant ileum. Results Enterocyte apoptosis was increased in waved-2 mice and prevented in bax-null mice after SBR. The accelerated apoptosis in the waved-2 mice was rescued in the context of deficient bax expression. Other parameters of adaptation were restored in the bax-null/waved-2 mice. Conclusion Bax is required for the induction of postresection enterocyte apoptosis. Defective EGFR signaling augments resection-induced enterocyte apoptosis via a mechanism that also requires bax expression. These data implicate a link between EGFR signaling and bax in the genesis of postresection apoptosis and adaptation.
AB - Background Adaptation after massive smallbowel resection (SBR) is associated with increased cell turnover, increased rates of enterocyte proliferation, and apoptosis. Epidermal growth factor receptor (EGFR) inhibition attenuates adaptation and increases apoptosis. Intestinal levels of bax appear to correlate with EGFR signaling. This study tested the hypothesis that bax is required for the exaggerated postresection apoptosis induced by perturbed EGFR signaling. Methods Waved-2 mice with impaired EGFR signaling were crossbred with bax-null mice. Offspring were subjected to either 50% proximal SBR or sham operation (bowel transection and reanastomosis). After 7 days, parameters of adaptation (villus height, wet weight), proliferation (% Ki-67 immunostaining of crypt cells), and apoptosis (# apoptotic bodies per crypt) were recorded in the remnant ileum. Results Enterocyte apoptosis was increased in waved-2 mice and prevented in bax-null mice after SBR. The accelerated apoptosis in the waved-2 mice was rescued in the context of deficient bax expression. Other parameters of adaptation were restored in the bax-null/waved-2 mice. Conclusion Bax is required for the induction of postresection enterocyte apoptosis. Defective EGFR signaling augments resection-induced enterocyte apoptosis via a mechanism that also requires bax expression. These data implicate a link between EGFR signaling and bax in the genesis of postresection apoptosis and adaptation.
UR - http://www.scopus.com/inward/record.url?scp=3843060138&partnerID=8YFLogxK
U2 - 10.1016/j.surg.2004.04.004
DO - 10.1016/j.surg.2004.04.004
M3 - Article
C2 - 15300170
AN - SCOPUS:3843060138
SN - 0039-6060
VL - 136
SP - 121
EP - 126
JO - Surgery
JF - Surgery
IS - 2
ER -