A defective EGF-receptor in waved-2 mice attenuates intestinal adaptation
A defective EGF-receptor in waved-2 mice attenuates intestinal adaptation
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DOI：
10.1006/jsre.1997.5033
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发表时间：
1997-04-01
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;Erwin, CR;Warner, BW
虽然小肠切除术（SBR）后肠适应的病理生理学尚未完全了解，但有证据表明表皮生长因子（EGF）在此过程中发挥重要作用，在wave-2小鼠中，天然发生的突变导致EGF受体蛋白酪氨酸激酶活性降低。我们测试的假设，一个完整的EGF受体是必不可少的适应这一品系的小鼠进行SBR。在wave-2、杂合子和野生型小鼠中进行50%近端SBR或假手术（仅肠横断再吻合）。3天后，适应的特点是在残余回肠的DNA和蛋白质含量每单位长度的变化。测量绒毛高度、酸隐窝深度，以隐窝细胞摄取5-溴脱氧尿苷的百分比测定隐窝细胞增殖率。假手术后，所有小鼠在术后第三天恢复其术前体重。SBR后，所有小鼠体重增加，而wave-2小鼠没有。回肠DNA和蛋白质显着增加后SBR在野生型和杂合子小鼠，而这些参数在wave-2小鼠无变化。绒毛高度和隐窝细胞增殖增加，在所有组中的SBR反应，但是，变化不太明显，在波-2小鼠。SBR后的适应在wave-2小鼠中受损。EGF受体的信号转导是这种反应的关键组成部分。这些数据证实了EGF及其受体在肠道适应性发病机制中的关键作用，（C）1997年学术出版社。
While the pathophysiology of intestinal adaptation following small bowel resection (SBR) is not well understood, there is evidence to suggest an important role for epidermal growth factor (EGF) in this process, in waved-2 mice, a naturally occurring mutation resuits in reduced EGF receptor protein tyrosine kinase activity. We tested the hypothesis that an intact EGF receptor is essential for adaptation by subjecting this strain of mice to SBR. A 50% proximal SBR or sham operation (bowel transection with reanastomosis only) was performed in waved-2, heterozygous, and wild-type mice. After 3 days, adaptation was characterized in the remnant ileum as changes in DNA and protein content per unit length. Villus height acid crypt depth were measured, and crypt cell proliferation rates were determined by the percentage of crypt cells taking up 5-bromodeoxyuridine. Following sham surgery, all mice regained their preoperative weight by the third postoperative day. After SBR, all mice gained weight while the waved-2 mice did not. Ileal DNA and protein significantly increased after SBR in wild-type and heterozygous mice while these parameters were unchanged in the waved-2 mice. Villus height and crypt cell proliferation increased in response to SBR in all groups; however, the changes were less pronounced in the waved-2 mice. Adaptation after SBR is impaired in waved-2 mice. Signal transduction by the EGF receptor is a critical component of this response. These data endorse a crucial role for EGF and its receptor in the pathogenesis of intestinal adaptation, (C) 1997 Academic Press.