Loss of the major duodenal papilla results in brown pigment biliary stone formation in pdx1 null mice
Loss of the major duodenal papilla results in brown pigment biliary stone formation in pdx1 null mice
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DOI：
10.1053/j.gastro.2005.11.031
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发表时间：
2006-03-01
期刊：
影响因子：
29.4
通讯作者：
Chiba, T
中科院分区：
文献类型：
--
作者：
Fukuda, A;Kawaguchi, Y;Chiba, T
背景与目的：Pdx 1在胰腺器官发生和十二指肠及胃窦胃某些类型细胞的特化中起关键作用。然而，它的表达不仅限于胰腺，十二指肠，胃窦胃，但也发现在胚胎发育过程中的胆总管。本研究旨在阐明Pdx 1在胆总管、十二指肠乳头和十二指肠发育中的作用。研究方法：分析pdx 1基因敲除小鼠胚胎发育过程中pdx 1的表达模式以及胆总管、十二指肠乳头和十二指肠的形态。结果：pdx基因敲除小鼠十二指肠乳头、胆周腺和胆总管内的粘液分泌细胞均未形成。在出生后阶段，Pdx1基因敲除小鼠的壶腹周围十二指肠绒毛比野生型小鼠短，这与十二指肠上皮细胞增殖减少和凋亡增加有关。十二指肠乳头的缺失导致十二指肠胆汁反流和胆汁感染，导致pdx 1基因敲除小鼠形成棕色胆结石，抗生素治疗显著降低了胆结石形成的发生率。结论：Pdx1是必需的十二指肠乳头，胆管周围的腺体，并在胆总管中的粘蛋白产生细胞的适当发展和维持的壶腹周围的十二指肠上皮细胞在围产期。十二指肠乳头缺失引起的胆汁感染在pdx1基因敲除小鼠中棕色胆结石的形成中起重要作用。
Background & Aims: Pdx1 plays a pivotal role in pancreas organogenesis and specification of some types of cells in the duodenum and antral stomach. However, its expression is not restricted to pancreas, duodenum, and antral stomach but is also found in the common bile duct during embryogenesis. This study aimed to elucidate the role of Pdx1 in the development of the common bile duct, major duodenal papilla, and duodenum. Methods: Expression pattern of pdx1 during embryogenesis and the morphology of the common bile duct, major duodenal papilla, and duodenum in pdx1 null mice were analyzed. Results: The major duodenal papilla, peribiliary glands, and mucin-producing cells in the common bile duct were not formed in pdx1 null mice. Pdx1 null mice had shorter periampullary duodenal villi than wildtype mice at postnatal stages associated with reduced cell proliferation and increased apoptosis of the duodenal epithelial cells. Loss of the major duodenal papilla allowed duodeno-biliary reflux and bile infection, resulting in the formation of brown pigment biliary stones in pdx1 null mice, and antibiotics treatment significantly reduced the incidence of biliary stone formation. Conclusions: Pdx1 is required for proper development of the major duodenal papilla, peribiliary glands, and mucin-producing cells in the common bile duct and for maintenance of the periampullary duodenal epithelial cells during perinatal period. Bile infection because of loss of the major duodenal papilla plays a significant role in the formation of brown pigment biliary stones in pdx1 null mice.