The fibroblast growth factor pathway serves a regulatory role in proliferation and apoptosis in the pathogenesis of intestinal atresia
The fibroblast growth factor pathway serves a regulatory role in proliferation and apoptosis in the pathogenesis of intestinal atresia
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DOI：
10.1016/j.jpedsurg.2005.10.054
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发表时间：
2006-01-01
影响因子：
2.4
通讯作者：
Burns, RC
中科院分区：
文献类型：
--
作者：
Fairbanks, TJ;Sala, FG;Burns, RC
背景/目的：肠道闭锁发生率为1:50 000，是新生儿的一大挑战。成纤维细胞生长因子受体2b （Fgfr2b）是包括胃肠道（GIT）在内的多器官系统中增殖和凋亡的关键发育调节剂。Fgfr2b失能导致常染色体隐性肠闭锁表型。本研究评估Fgfr2b信号在肠闭锁发病机制中调控增殖和凋亡的作用。方法：从定时妊娠小鼠中获取野生型和Fgfr2b（-/-）胚胎。使用标准技术获取GIT。用末端脱氧核苷酸转移酶生物素（dutp）评价细胞凋亡，用溴脱氧尿苷评价细胞增殖。比较显微照片（机构动物护理和使用委员会批准的方案32-02）。结果：野生型和突变型GIT表明，Fgfr2b基因的缺失导致上皮细胞增殖抑制和细胞凋亡增加。增殖抑制和凋亡增加是Fgfr2b表达正常的组织所特有的，与肠闭锁部位相对应。结论：胚胎GIT Fgfr2b表达缺失导致GIT细胞增殖减少，细胞凋亡增加，导致GIT闭锁。肠细胞增殖和凋亡的调控作为肠闭锁的遗传原因，代表了肠闭锁发病机制的一个新的考虑。(c) 2006爱思唯尔公司版权所有。
Background/Purpose: Intestinal atresia occurs in 1:5000 live births and is a neonatal challenge. Fibroblast growth factor receptor 2b (Fgfr2b) is a critical developmental regulator of proliferation and apoptosis in multiple organ systems including the gastrointestinal tract (GIT). Fgfr2b invalidation results in an autosomal recessive intestinal atresia phenotype. This study evaluates the role of Fgfr2b signaling in regulating proliferation and apoptosis in the pathogenesis of intestinal atresia.Methods: Wild-type and Fgfr2b(-/-) embryos were harvested from timed pregnant mice. The GIT was harvested using standard techniques. Terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling) was used to evaluate apoptosis and bromodeoxyuridine to assess proliferation by standard protocols. Photomicrographs were compared (institutional Animal Care and Use Committee-approved protocol 32-02).Results: Wild-type and mutant GIT demonstrate that deletion of the Fgfr2b gene results in inhibition of epithelial proliferation and increased apoptosis. Inhibited proliferation and increased apoptosis are specific to those tissues of normal Fgfr2b expression, corresponding to the site of intestinal atresia.Conclusions: The absence of embryonic GIT Fgfr2b expression results in decreased proliferation and increased apoptosis resulting in GIT atresia. The regulation of proliferation and apoptosis in intestinal cells as a genetically based cause of intestinal atresia represents a novel consideration in the pathogenesis of intestinal atresia. (c) 2006 Elsevier Inc. All rights reserved.