Downregulation of Notch-1/Jagged-2 in human colon tissues from Hirschsprung disease patients
Downregulation of Notch-1/Jagged-2 in human colon tissues from Hirschsprung disease patients
复制标题
先天性巨结肠症患者的人结肠组织中 Notch-1/Jagged-2 的下调
DOI：
10.1007/s00384-011-1295-4
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发表时间：
2012-01-01
影响因子：
2.8
通讯作者：
Wang, Weilin
中科院分区：
文献类型：
--
作者：
Jia, Huimin;Zhang, Keren;Wang, Weilin
目的 近期研究表明，Notch通路在神经元的分化和发育中起重要作用。先天性巨结肠症（HSCR）的特征是远端肠道神经丛中缺乏肠壁内神经节细胞。然而，Notch在肠神经系统（ENS）发育中的假定功能以及HSCR的病因尚不清楚。
材料与方法 对30例HSCR患者的无神经节细胞段进行研究，采用免疫组织化学染色、逆转录聚合酶链反应（RT - PCR）和蛋白质印迹分析来探究Notch - 1和Jagged - 2的表达模式。
结果 在正常或神经节细胞减少段的黏膜下层和肌间神经丛中检测到强烈的Notch - 1和Jagged - 2染色。HSCR患者的无神经节细胞段没有神经丛，因此未被Notch - 1和Jagged - 2标记。蛋白质印迹分析显示HSCR患者无神经节细胞段的Notch - 1和Jagged - 2蛋白水平降低，RT - PCR显示其Notch - 1和Jagged - 2 mRNA降低。
结论 本研究首次阐述了Notch - 1和Jagged - 2在非癌性疾病人体组织中的表达，为进一步研究Notch在ENS发育和肠道动力中的功能奠定了基础。
PurposeRecent studies have shown that the Notch pathways play important roles in the differentiation and development of neurons. Hirschsprung disease (HSCR) is characterized by the absence of intramural ganglion cells in the nerve plexuses of the distal gut. However, putative Notch function in enteric nervous system (ENS) development and the etiology of HSCR is unknown.Materials and methodsThe aganglionosis segments of 30 HSCR patients were introduced to investigate the expression pattern of Notch-1 and Jagged-2 using immunohistochemical staining, reverse transcriptase polymerase chain reaction (RT-PCR), and Western blot analysis.ResultsIntensive Notch-1 and Jagged-2 staining was detected in the submucosal and the myenteric plexuses in normal or oligoganglionosis segments. Aganglionosis segments from HSCR patients contained no plexuses and thus not labeled with Notch-1 and Jagged-2. Western blot analysis revealed reduced Notch-1 and Jagged-2 protein levels, and RT-PCR revealed reducedNotch-1andJagged-2mRNA in the aganglionosis segments of HSCR patients.ConclusionsThis study is the first illustration of Notch-1 and Jagged-2 expression in human tissues from non-cancerous disease and sets up the base for further investigations of Notch function in ENS development and intestinal motility.