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人抗原 R:肝脏疾病的潜在治疗靶点。

Human antigen R: A potential therapeutic target for liver diseases.

机构信息

School of Chinese Materia Medica, Beijing University of Chinese Medicine, 11 Bei San Huan Dong Lu, Beijing, 100029, China.

The Second Hospital of Shandong University, 247 Bei Yuan Da Jie, Jinan, 250033, China.

出版信息

Pharmacol Res. 2020 May;155:104684. doi: 10.1016/j.phrs.2020.104684. Epub 2020 Feb 8.

Abstract

Human antigen R (HuR), also known as HuA and embryonic lethal abnormal vision-like 1 (ELAVL1), is a ubiquitously expressed RNA binding protein and functions as an RNA regulator and mediates the expression of various proteins by diverse post-transcriptional mechanisms. HuR has been well characterized in the inflammatory responses and in the development of various cancers. The importance of HuR-mediated roles in cell signaling, inflammation, fibrogenesis and cancer development in the liver has attracted a great deal of attention. However, there is still a substantial gap between the current understanding of the potential roles of HuR in the progression of liver disease and whether HuR can be targeted for the treatment of liver diseases. In this review, we introduce the function and mechanistic characterization of HuR, and then focus on the physiopathological roles of HuR in the development of different liver diseases, including hepatic inflammation, alcoholic liver diseases, non-alcoholic fatty liver diseases, viral hepatitis, liver fibrosis and liver cancers. We also summarize existing approaches targeting HuR function. In conclusion, although characterizing the liver-specific HuR function and demonstrating the multi-level regulative networks of HuR in the liver are still required, emerging evidence supports the notion that HuR represents a potential therapeutic target for the treatment of chronic liver diseases.

摘要

人抗原 R(HuR),也称为 HuA 和胚胎致死异常视觉样 1(ELAVL1),是一种广泛表达的 RNA 结合蛋白,作为 RNA 调节剂发挥作用,并通过各种转录后机制调节各种蛋白质的表达。HuR 在炎症反应和各种癌症的发展中得到了很好的描述。HuR 介导的细胞信号转导、炎症、纤维化和癌症发展中的作用的重要性引起了极大的关注。然而,目前对 HuR 在肝病进展中的潜在作用的理解与 HuR 是否可作为治疗肝病的靶点之间仍然存在很大差距。在这篇综述中,我们介绍了 HuR 的功能和机制特征,然后重点介绍了 HuR 在不同肝病发展中的生理病理作用,包括肝炎症、酒精性肝病、非酒精性脂肪性肝病、病毒性肝炎、肝纤维化和肝癌。我们还总结了现有的靶向 HuR 功能的方法。总之,尽管仍需要对肝脏特异性 HuR 功能进行表征,并证明 HuR 在肝脏中的多层次调节网络,但新出现的证据支持 HuR 是治疗慢性肝病的潜在治疗靶点的观点。

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