Emerging roles of Notch signaling in liver disease.
Emerging roles of Notch signaling in liver disease.
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DOI：
10.1002/hep.27268
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发表时间：
2015-01
期刊：
影响因子：
13.5
通讯作者：
Strazzabosco, Mario
中科院分区：
文献类型：
--
作者：
Geisler, Fabian;Strazzabosco, Mario
这篇综述批判性地讨论了 Notch 信号在肝脏发育、稳态和疾病中作用的最新进展。现在很清楚，Notch 在决定哺乳动物细胞命运和功能方面的重要性超出了发育范围，而且 Notch 是器官稳态的主要调节因素。此外，Notch 信号传导在损伤后会重新激活，并调节参与修复过程的不同细胞类型之间复杂的相互作用。 Notch还参与肝脏代谢、炎症和癌症的调节。 Notch 信号传导的净效应是高度可变的，并且在多个层面上受到精细调节，但也取决于 Notch 被激活的特定细胞环境。 Notch信号的持续激活与肝脏恶性肿瘤有关，例如具有干细胞特征的肝细胞癌和肝内胆管癌。该途径的复杂性为能够抑制 Notch 的药物提供了几个可能的靶点。然而，进一步深入了解肝脏稳态和疾病中的 Notch 信号传导，对于将这些概念转化为临床实践并能够预测不断发展的疗法的益处和风险至关重要。
This review critically discusses the most recent advances on the role of Notch signaling in liver development, homeostasis and disease. It is now clear that the significance of Notch in determining mammalian cell fates and functions extends beyond development, and Notch is a major regular of organ homeostasis. Moreover, Notch signaling is reactivated upon injury and regulates the complex interactions between the distinct cellular types involved in the repair process. Notch is also involved in the regulation of liver metabolism, inflammation and cancer. The net effects of Notch signaling are highly variable and finely regulated at multiple levels, but also depend on the specific cellular context in which Notch is activated. Persistent activation of Notch signaling is associated with liver malignancies, such as hepatocellular carcinoma with stem cell features and intrahepatic cholangiocarcinoma. The complexity of the pathway provides several possible targets for agents able to inhibit Notch. However, further cell- and context-specific in depth understanding of Notch signaling in liver homeostasis and disease will be essential to translate these concepts into the clinical practice and be able to predict benefits and risks of evolving therapies.
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