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首页> 外文期刊>Cellular Physiology and Biochemistry >Inhibition of the Notch Signaling Pathway Reduces the Differentiation of Hepatic Progenitor Cells into Cholangiocytes in Biliary Atresia
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Inhibition of the Notch Signaling Pathway Reduces the Differentiation of Hepatic Progenitor Cells into Cholangiocytes in Biliary Atresia

机译：Notch信号通路的抑制减少胆道闭锁中肝祖细胞分化为胆管细胞。

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Background/Aims Viral infections, especially with rotavirus, are often considered an initiator of the pathogenesis of biliary atresia (BA). However, the mechanism by which rotavirus induces BA is still unclear. Methods A BA mouse model was induced in newborn mice by i.p. inoculation with rhesus rotavirus within 6 h of birth. The expression of Notch pathway-associated molecules (JAG1, JAG2, Notch1, Notch2, Notch3, Notch4, DII1, DII3, and DII4) was measured by quantitative PCR and western blot analysis. Bile duct obstruction was detected by hematoxylin and eosin staining and CK-19 immunohistochemical staining. DAPT was used to inhibit the Notch pathway in vivo and in vitro. Results In the livers of patients with BA and rotavirus-induced BA mice, the expression of JAG1 and Notch2 was significantly increased. Inhibition of the Notch pathway by DAPT in vivo ameliorated bile duct obstruction and delayed BA-induced mortality. The serum levels of inflammation cytokines (TNF-α, IL-2, IL-8, and IL-18) were reduced by inhibiting the Notch pathway. The expression of CK19, Sox9, and EpCAM was significantly increased in BA liver, while DAPT treatment decreased the expression of CK19, Sox9, and EpCAM. Conclusion Notch activation is involved in the pathogenesis of BA by promoting the differentiation of hepatic progenitor cells into cholangiocytes.
机译：背景/目的病毒感染，特别是轮状病毒感染，通常被认为是胆道闭锁（BA）发病机制的引发者。但是，轮状病毒诱导BA的机制仍不清楚。方法通过腹腔注射法在新生小鼠体内建立BA小鼠模型。出生后6小时内接种恒河猴轮状病毒。通过定量PCR和western印迹分析测量与Notch途径相关的分子（JAG1，JAG2，Notch1，Notch2，Notch3，Notch4，DII1，DII3和DII4）的表达。苏木和曙红染色及CK-19免疫组化染色检测胆管阻塞。 DAPT用于体内和体外抑制Notch途径。结果在BA和轮状病毒诱导的BA小鼠的肝脏中，JAG1和Notch2的表达明显增加。 DAPT在体内抑制Notch途径可改善胆管阻塞并延缓BA诱发的死亡率。通过抑制Notch途径，降低了血清炎症细胞因子（TNF-α，IL-2，IL-8和IL-18）的水平。 BA肝脏中CK19，Sox9和EpCAM的表达显着增加，而DAPT处理则降低了CK19，Sox9和EpCAM的表达。结论Notch激活通过促进肝祖细胞向胆管细胞的分化而参与BA的发病过程。

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