The EGF\EGF-receptor axis modulates enterocyte apoptosis during intestinal adaptation
The EGF\EGF-receptor axis modulates enterocyte apoptosis during intestinal adaptation
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DOI：
10.1006/jsre.1998.5362
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发表时间：
1998-06-01
影响因子：
2.2
通讯作者：
Warner, BW
中科院分区：
文献类型：
--
作者：
Helmrath, MA;Shin, CE;Warner, BW
背景小肠切除术（SBR）后适应的特点是肠上皮细胞增殖和凋亡平衡的新设定点。由于表皮生长因子（EGF）增强增殖和适应，我们试图确定表皮生长因子受体操作对SBR后细胞凋亡的影响。雄性ICR小鼠进行50%SBR或假手术（肠横断再吻合），然后通过口胃管饲给予EGF（50 μ g/kg/天）或盐水。在1周时，通过BrdU摄取测量回肠中的增殖指数（PI），并通过计数肠细胞中的凋亡小体来对隐窝（cAI）和绒毛（vAI）中的凋亡指数进行评分。在其他实验中，在具有缺陷受体（waved-2）的小鼠中，在SBR后对AI进行评分。结果表示为平均值+/- SE，并使用ANOVA进行统计学评价。#表示P <0.001。SBR后，EGF增加PI（40 +/-2%vs 50 +/-1%BrdU+细胞; #）、绒毛高度（252 +/- 4 μ m vs 401 +/- 15 μ m; #）和隐窝深度（77.3 +/- 1.5 μ m vs 120.8 +/- 5 μ m; #）。与假手术组相比，SBR导致cAI（0.3 +/- 0.02 vs 2.0 +/- 0.1; #）和vAI（0.4 +/- 0.05 vs 1.1 +/- 0.1; #）增加。EGF减弱SBR后的cAI（0.5 +/- 0.04）和vAI（0.5 +/- 0.03）。在wave-2小鼠中，在SBR后观察到最高水平的cAI（3.1 +/- 0.2）和vAI（3.6 +/- 0.3）。肠上皮细胞凋亡在适应过程中被EGF减弱，并在EGF受体缺陷时被夸大。除了促进增殖，抑制细胞凋亡可能提供了一个以前未被认识的机制，在肠适应过程中的有益作用的EGF。(C)北京：科学出版社.
Background. Adaptation after small bowel resection (SBR) is characterized by a new set point in the balance of enterocyte proliferation and apoptosis. Since epidermal growth factor (EGF) augments both proliferation and adaptation, we sought to determine the effect of EGF receptor manipulation on apoptosis following SBR.Materials and Methods. Male ICR mice underwent 50% SBR or sham operation (bowel transection with reanastomosis) and then were given EGF (50 mu g/kg/day) or saline by orogastric gavage. At 1 week, a proliferation index (PI) was measured in the ileum by BrdU uptake and an apoptosis index in crypts (cAI) and villi (vAI) scored by counting apoptotic bodies in enterocytes. In other experiments, AI was scored after SBR in mice with defective receptors (waved-2). Results are expressed as means +/- SE and evaluated statistically using ANOVA. # denotes P < 0.001.Results. Following SBR, EGF increased PI (40 +/- 2% vs 50 +/- 1% BrdU + cells; #), villus height (252 +/- 4 mu m vs 401 +/- 15 mu m; #), and crypt depth (77.3 +/- 1.5 mu m vs 120.8 +/- 5 mu m; #). When compared with sham, SBR resulted in increased cAI (0.3 +/- 0.02 vs 2.0 +/- 0.1; #) and vAI (0.4 +/- 0.05 vs 1.1 +/- 0.1; #). EGF attenuated both cAI (0.5 +/- 0.04) and vAI (0.5 +/- 0.03) following SBR. In the waved-2 mice, the highest levels of cAI (3.1 +/- 0.2) and vAI (3.6 +/- 0.3) were noted after SBR.Conclusions. Enterocyte apoptosis during adaptation is attenuated by EGF and exaggerated when the EGF receptor is defective. In addition to enhancing proliferation, suppression of apoptosis may provide a previously unrecognized mechanism for the beneficial effect of EGF during intestinal adaptation. (C) 1998 Academic Press.