Department of Surgery and Interdisciplinary Medicine, University of Milano-Bicocca, Milan, Italy.
Department of Surgery and Interdisciplinary Medicine, University of Milano-Bicocca, Milan, Italy; Liver Center & Section of Digestive Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA.
J Hepatol. 2014 Apr;60(4):885-90. doi: 10.1016/j.jhep.2013.11.028. Epub 2013 Dec 3.
Notch signaling is a crucial determinant of cell fate decision during development and disease in several organs. Notch effects are strictly dependent on the cellular context in which it is activated. In the liver, Notch signaling is involved in biliary tree development and tubulogenesis. Recent advances have shed light on Notch as a critical player in liver regeneration and repair, as well as in liver metabolism and inflammation and cancer. Notch signaling is finely regulated at several levels. The complexity of the pathway provides several possible targets for development of therapeutic agents able to inhibit Notch. Recent reports have shown that persistent activation of Notch signaling is associated with liver malignancies, particularly hepatocellular with stem cell features and cholangiocarcinoma. These novel findings suggest that interfering with the aberrant activation of the Notch pathway may have therapeutic relevance. However, further studies are needed to clarify the mechanisms regulating physiologic and pathologic Notch activation in the adult liver, to better understand the mechanistic role(s) of Notch in liver diseases and to develop safe and specific therapeutic agents.
Notch 信号通路是决定多种器官发育和疾病中细胞命运的关键因素。Notch 的作用严格依赖于其激活的细胞环境。在肝脏中，Notch 信号通路参与胆管树发育和小管形成。最近的研究进展表明，Notch 是肝脏再生和修复以及肝脏代谢、炎症和癌症的关键参与者。 Notch 信号通路在多个水平上受到精细调控。该途径的复杂性为开发能够抑制 Notch 的治疗药物提供了几个可能的靶点。最近的报告表明， Notch 信号的持续激活与肝恶性肿瘤有关，特别是具有干细胞特征的肝细胞癌和胆管细胞癌。这些新发现表明，干扰 Notch 途径的异常激活可能具有治疗相关性。然而，需要进一步的研究来阐明调节成年肝脏中生理和病理 Notch 激活的机制，以更好地了解 Notch 在肝脏疾病中的作用机制，并开发安全和特异的治疗药物。
