Colonic atresia without mesenteric vascular occlusion. The role of the fibroblast growth factor 10 signaling pathway
Colonic atresia without mesenteric vascular occlusion. The role of the fibroblast growth factor 10 signaling pathway
复制标题
DOI：
10.1016/j.jpedsurg.2004.10.023
复制
发表时间：
2005-02-01
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;Kanard, RC;Burns, RC
背景/目的：结肠闭锁发生率为1:20 000，给新生儿手术带来了挑战。产前表达成纤维细胞生长因子10 (Fgf10)，通过成纤维细胞生长因子受体2b （Fgfr2b）起作用，对结肠的正常发育至关重要。Fgf10通路的失效导致结肠闭锁，以常染色体隐性模式遗传。传统上，肠系膜血管系统紊乱被认为是多种形式的肠闭锁的原因。本研究的目的是评估血管阻塞在结肠闭锁发病机制中的作用。方法：获取野生型（Wt）、Fgf10（-/-）和Fgf10（-/-）突变小鼠胚胎。收获后，立即通过心脏内显微注射注入过滤后的印度墨水。解剖胃肠道，并在关键发育时间点拍摄肠系膜动脉解剖的显微照片。结果：印度墨水显微注射后的显微照片显示，在Fgf10（-/-）和Fgfr2b（-/-）突变体结肠发育失败对应的时间点上，正常的、通畅的肠系膜级联到闭锁结肠。结肠肠系膜动脉解剖显示Wt型和突变型结肠闭锁无差异。结论：胚胎期缺乏Fgf10或其受体Fgfr2b表达可导致小鼠结肠闭锁。印墨显微注射是肠系膜动脉通畅的直接测量方法。尽管肠系膜血管发育正常，Fgf10（-/-）和Fgfr2b（-/-）突变体仍会发生结肠闭锁。因此闭锁不是肠系膜血管闭塞的结果。Fgf10（-/-）和Fgfr2b（-/-）突变体的结肠肠系膜未闭挑战了公认的肠闭锁发病机制。虽然结肠闭锁可因血管闭塞而发生，但新的证据表明，遗传机制可能在这种疾病的发病机制中起作用。(C) 2005爱思唯尔公司版权所有。
Background/Purpose: Colonic atresia occurs in 1:20,000 live births, offering a neonatal surgical challenge. Prenatal expression of fibroblast growth factor 10 (Fgf10), acting through fibroblast growth factor receptor 2b (Fgfr2b), is critical to the normal development of the colon. Invalidation of the Fgf10 pathway results in colonic atresia, inherited in an autosomal recessive pattern. Classically, disturbance of the mesenteric vasculature has been thought to cause many forms of intestinal atresia. The purpose of this study was to evaluate the role of vascular occlusion in the pathogenesis of colonic atresia.Methods: Wild type (Wt), Fgf10(-/-), and Fgf10(-/-) mutant mouse embryos were harvested from timed pregnant mothers. Immediately following harvest, filtered India ink was infused via intracardiac microinjection. The gastrointestinal tract was dissected, and photomicrographs of the mesenteric arterial anatomy were taken at key developmental time points.Results: Photomicrographs after India ink microinjections demonstrate normal, patent mesenteric cascades to the atretic colon at the time points corresponding to the failure of colonic development in the Fgf10(-/-) and Fgfr2b(-/-) mutants. The mesenteric arterial anatomy of the colon demonstrates no difference between the Wt and mutant colonic atresia.Conclusions: The absence of embryonic expression of Fgf10 or its receptor Fgfr2b results in colonic atresia in mice. India ink microinjection is a direct measure of mesenteric arterial patency. Colonic atresia in the Fgf10(-/-) and Fgfr2b(-/-) mutants occurs despite normal mesenteric vascular development. Thus the atresia is not the result of a mesenteric vascular occlusion. The patent colonic mesentery of the Fgf10(-/-) and Fgfr2b(-/-) mutants challenges an accepted pathogenesis of intestinal atresia. Although colonic atresia can occur as a result of vascular occlusion, new evidence exists to suggest that a genetic mechanism may play a role in the pathogenesis of this disease. (C) 2005 Elsevier Inc. All rights reserved.