Wnt信号通路与肝再生的关系及其在肝脏疾病中的作用
DOI: 10.12449/JCH240529
The relationship between the Wnt signaling pathway and liver regeneration and its role in liver diseases
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摘要: Wnt信号通路在维持肝脏内稳态和肝脏再生过程中扮演重要角色,在成熟的健康肝脏中,Wnt信号通路大多是不活跃的,但在细胞更新或再生过程中,以及在某些病理条件、疾病、癌前状态和癌症中,Wnt信号通路被持续过度激活。持续的肝细胞损伤常常会导致慢性肝病,如肝纤维化、肝硬化及肝癌等。本文概述了Wnt信号通路的基本结构特点,详细分析了其在多种肝脏疾病病理进展所扮演的重要角色,希望为临床防治肝脏疾病提供新思路。Abstract: The Wnt signaling pathway plays an important role in maintaining liver homeostasis and liver regeneration. In healthy livers, the Wnt signaling pathway is mostly inactive, but it is continuously overactivated during cell renewal or regeneration processes, as well as in certain pathological conditions, diseases, precancerous states, and cancers. Persistent liver cell injury often leads to chronic liver diseases such as liver fibrosis, liver cirrhosis, and liver cancer. This article summarizes the basic structural features of the Wnt signaling pathway and analyzes its important role in the pathological progression of various liver diseases, so as to provide new ideas for the prevention and treatment of liver diseases in clinical practice.
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Key words:
- Liver Diseases /
- Liver Regeneration /
- Wnt Signaling Pathway /
- beta Catenin
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表 1 针对Wnt/β-catenin信号传导的药物临床试验
Table 1. Clinical trials of agents targeting Wnt/β-catenin signalling
药物 类型 靶点 作用 阶段 临床试验记录 LGK974(WNT974) 融合蛋白 Wnt配体 FZD8融合蛋白与FZD8竞争结合Wnt配体 Ⅰ期 NCT01608867,NCT02050178, NCT02069145,NCT02092363 OMP-131R10 单抗 R-spondin 3 抑制 RSPO-LGR-ZNRF3/RNF43复合体 Ⅰ期 NCT02482441 OTSA101 单抗 FZD10 抗FZD10型单抗 Ⅰ期 NCT01469975 OMP-18R5 单抗 FZD受体 抗FZD受体型单抗 Ⅰ期 NCT01345201,NCT01957007, NCT01973309,NCT02005315 DKN-01 单抗 DKK1 抗DKK1型单抗,抑制非典型β-catenin传导途径 Ⅰ期, Ⅱ期 NCT01457417,NCT01711671, NCT02013154,NCT02375880 BHQ880 单抗 DKK1 抗DKK1型单抗,抑制非典型β-catenin传导途径 Ⅰ期, Ⅱ期 NCT00741377,NCT01302886, NCT01337752 Foxy-5 小肽 FZD受体 Wnt 5a类似物 Ⅰ期 NCT02020291,NCT02655952 PRI 724 小分子 β-catenin, CREB结合蛋白 下调β-catenin反应基因 Ⅰ期, Ⅱ期 NCT01302405,NCT01606579, NCT01764477,NCT02195440 SM08502 小分子 未知 抑制β-catenin传导途径 Ⅰ期 NCT03355066 -
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