期刊
JOURNAL OF PEDIATRIC SURGERY
卷 38, 期 6, 页码 875-879出版社
W B SAUNDERS CO
DOI: 10.1016/S0022-3468(03)00114-3
关键词
apoptosis; bax; bcl-2; epidermal growth factor receptor signaling; small bowel resection; enterectomy; mice
资金
- NIDDK NIH HHS [R01 DK 59288, R01 DK53234] Funding Source: Medline
- NIGMS NIH HHS [T32 GM 08478] Funding Source: Medline
Background. After massive small bowel resection (SBR), enterocyte apoptosis is elevated and inversely correlates with epidermal growth factor receptor (EGFR) signaling. The purpose of the current study was to determine whether EGFR manipulation affects the expression of specific bcl-2 family members. Methods: A 50% proximal SBR or sham operation was performed in 3 groups of mice control, after exogenous EGF, or mutant mice with defective EGFR signaling (waved-2). Apoptotic index (no. of apoptotic bodies per crypt), and bax (pro-apoptosis) and bcl-w (anti-apoptosis) protein expression was measured in the remnant ileum after 12, 24, and 72 hours. Results: Waved-2 mice with defective EGFR showed the greatest increase in apoptosis and altered the ratio of bax to bcl-w in favor of apoptosis after SBR. Conversely, EGF prevented the expected increase in apoptosis after SBR by shifting the ratio of bax to bcl-w in favor of cell survival. Conclusions: After massive small bowel resection, inhibition of the EGFR accelerates the rate of apoptosis and modifies the expression of specific bcl-2 family members to favor apoptosis. These results further support a specific mechanistic pathway for the regulation of enterocyte apoptosis after SBR via EGFR signaling. (C) 2003 Elsevier Inc. All rights reserved.
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