在肠细胞中过表达肝素结合表皮生长因子样生长因子转基因的小鼠的肠道表型
Intestinal phenotype in mice overexpressing a heparin-binding EGF-like growth factor transgene in enterocytes.
作者信息
Chen Chun-Liang, Mehta Veela B, Zhang Hong-Yi, Wu Dana, Otabor Iyore, Radulescu Andrei, El-Assal Osama N, Feng Jiexiong, Chen Yan, Besner Gail E
机构信息
Department of Pediatric Surgery, The Research Institute at Nationwide Children's Hospital, Center for Perinatal Research, Nationwide Children's Hospital, The Ohio State University College of Medicine, Columbus, OH, USA.
出版信息
Growth Factors. 2010 Apr;28(2):82-97. doi: 10.3109/08977190903407365.
Abstract
PRIMARY OBJECTIVE
Heparin-binding EGF-like growth factor (HB-EGF) protects the intestine from damage in animals. Future clinical trials of HB-EGF may involve administration of repeated doses of HB-EGF. Since HB-EGF activates EGF receptors which have been implicated in tumor development, we examined the effects of HB-EGF overexpression in the intestine.
RESEARCH DESIGN
We generated transgenic (TG) mice in which the human HB-EGF gene is driven by the villin promoter to overexpress HB-EGF along the crypt-villous axis from the duodenum to the colon.
RESULTS
HB-EGF TG mice have increased enterocyte proliferation balanced by increased enterocyte apoptosis. Despite prolonged overexpression of HB-EGF, no evidence of intestinal hyperplasia or tumor formation occurs. Although HB-EGF TG mice have no significant phenotypic alterations under basal conditions, they have increased resistance to intestinal injury.
CONCLUSIONS
Prolonged intestinal HB-EGF overexpression results in no significant phenotypic alterations under basal conditions, but confers protection against intestinal injury.
摘要
主要目的
肝素结合表皮生长因子（HB-EGF）可保护动物肠道免受损伤。未来HB-EGF的临床试验可能涉及重复给药HB-EGF。由于HB-EGF可激活与肿瘤发展有关的表皮生长因子受体，我们研究了HB-EGF在肠道中过表达的影响。
研究设计
我们构建了转基因（TG）小鼠，其中人HB-EGF基因由绒毛蛋白启动子驱动，从而沿十二指肠至结肠的隐窝-绒毛轴过表达HB-EGF。
结果
HB-EGF转基因小鼠肠上皮细胞增殖增加，同时肠上皮细胞凋亡也增加，二者达到平衡。尽管HB-EGF长期过表达，但未出现肠道增生或肿瘤形成的迹象。虽然HB-EGF转基因小鼠在基础条件下没有明显的表型改变，但它们对肠道损伤的抵抗力增强。
结论
在基础条件下，肠道长期过表达HB-EGF不会导致明显的表型改变，但可提供对肠道损伤的保护作用。
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