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Wnt 信号通路在肝纤维化中的新兴作用及治疗意义。

Emerging role and therapeutic implication of Wnt signaling pathways in liver fibrosis.

机构信息

Department of Education, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, 230022, Anhui Province, China.

Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, China.

出版信息

Gene. 2018 Oct 20;674:57-69. doi: 10.1016/j.gene.2018.06.053. Epub 2018 Jun 23.

Abstract

Activation of hepatic stellate cells (HSCs) is a pivotal cellular event in liver fibrosis. Therefore, improving our understanding of the molecular pathways that are involved in these processes is essential to generate new therapies for liver fibrosis. Greater knowledge of the role of the Wnt signaling pathway in liver fibrosis could improve understanding of the liver fibrosis pathogenesis. The aim of this review is to describe the present knowledge about the Wnt signaling pathway, which significantly participates in liver fibrosis and HSC activation, and look ahead on new perspectives of Wnt signaling pathway research. Moreover, we will discuss the different interactions with Wnt signaling pathway-regulated liver fibrosis. The Wnt signaling pathway modulates several important aspects of function, including cell proliferation, activation and differentiation. Targeting the Wnt signaling pathway can be a promising direction in liver fibrosis treatment. We discuss new perspectives of Wnt signaling pathway activation in liver fibrosis. For example, antagonist to Wnt and Wnt ligands could inhibit liver fibrosis by regulating Wnt/β-catenin signaling pathway. These findings identify the Wnt signaling pathway as a potentially important for therapeutic targets in liver fibrosis. Future studies are needed in order to find safer and more effective Wnt-based drugs.

摘要

肝星状细胞(HSCs)的激活是肝纤维化的关键细胞事件。因此,深入了解参与这些过程的分子途径对于开发肝纤维化的新疗法至关重要。更多地了解 Wnt 信号通路在肝纤维化中的作用可以加深对肝纤维化发病机制的理解。本综述旨在描述 Wnt 信号通路的现有知识,该通路显著参与肝纤维化和 HSC 激活,并展望 Wnt 信号通路研究的新视角。此外,我们将讨论与 Wnt 信号通路调节的肝纤维化的不同相互作用。Wnt 信号通路调节功能的几个重要方面,包括细胞增殖、激活和分化。靶向 Wnt 信号通路可能是肝纤维化治疗的一个有前途的方向。我们讨论了 Wnt 信号通路在肝纤维化中的新激活视角。例如,Wnt 拮抗剂和配体可以通过调节 Wnt/β-catenin 信号通路来抑制肝纤维化。这些发现将 Wnt 信号通路确定为肝纤维化治疗的潜在重要靶点。为了找到更安全、更有效的基于 Wnt 的药物,未来还需要进行更多的研究。

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