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Notch 信号通路在肝纤维化中的新认识。

Novel Insights on Notch signaling pathways in liver fibrosis.

机构信息

Department of Pharmacy, Children's Hospital of Nanjing Medical University, No.72 Guangzhou Road, Nanjing 210001,China.

TCM Research Institution, Nanjing Municipal Hospital of T.C.M, The Third Affiliated Hospital of Nanjing University of T.C.M, Nanjing 210001,China.

出版信息

Eur J Pharmacol. 2018 May 5;826:66-74. doi: 10.1016/j.ejphar.2018.02.051. Epub 2018 Mar 1.

Abstract

Liver fibrosis is characterized by an increased and altered deposition of extracellular matrix (ECM) proteins that make up excessive tissue scarring and promote chronic liver injury. Activation of hepatic stellate cells (HSCs) is a pivotal cellular event in the progression of liver fibrosis. However, the mechanisms involved in the development of liver fibrosis are only now beginning to be unveiled. The Notch pathway is a fundamental and highly conserved pathway able to control cell-fate, including cell proliferation, differentiation, apoptosis, regeneration and other cellular activities. Recently, the deregulation of Notch cascade has been found involved in many pathological processes, including liver fibrosis. These data give evidence for a role for Notch signaling in liver fibrosis. In addition,more and more date are available on the role of Notch pathways in the process. Therefore, this review focuses on the current knowledge about the Notch signaling pathway, which dramatically takes part in HSC activation and liver fibrosis, and look ahead on new perspectives of Notch signaling pathway research. Furthermore, we will summarize this new evidence on the different interactions in Notch signaling pathway-regulated liver fibrosis, and support the potentiality of putative biomarkers and unique therapeutic targets.

摘要

肝纤维化的特征是细胞外基质(ECM)蛋白的过度沉积和改变,这些蛋白构成了过多的组织瘢痕,并促进慢性肝损伤。肝星状细胞(HSCs)的激活是肝纤维化进展中的关键细胞事件。然而,肝纤维化发展中涉及的机制才刚刚开始被揭示。Notch 通路是一个基本的和高度保守的通路,能够控制细胞命运,包括细胞增殖、分化、凋亡、再生和其他细胞活动。最近, Notch 级联的失调已被发现参与许多病理过程,包括肝纤维化。这些数据为 Notch 信号在肝纤维化中的作用提供了证据。此外, Notch 途径在该过程中的作用有越来越多的数据支持。因此,本综述重点介绍 Notch 信号通路的最新知识, Notch 信号通路在 HSC 激活和肝纤维化中起着重要作用,并展望 Notch 信号通路研究的新前景。此外,我们将总结 Notch 信号通路调节肝纤维化的不同相互作用的新证据,并支持潜在的生物标志物和独特的治疗靶点。

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