蛋白质二硫键异构酶血栓疾病致病机制研究进展

王俐尧; 王秉坤; 李文; 阿依买力卡·阿日甫; 白天雨; 许萌; 苏利波

doi:10.16766/j.cnki.issn.1674-4152.002782

蛋白质二硫键异构酶血栓疾病致病机制研究进展

doi: 10.16766/j.cnki.issn.1674-4152.002782

1.
河北医科大学实验动物学部，河北省实验动物学重点实验室，河北石家庄 050017
2.
哈尔滨医科大学附属第四医院病理科，黑龙江哈尔滨 150001

基金项目:

河北省高等学校科学技术研究项目 BJ2019026

详细信息

通讯作者:
苏利波，E-mail：116571383@qq.com

中图分类号: R543.31
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- 被引次数: 0
出版历程
- 收稿日期: 2022-06-08
- 网络出版日期: 2023-02-07

Advances in pathogenesis of protein disulfide isomerase in thrombotic disease

1.
Department of Laboratory Animal, Hebei Medical University, Shijiazhuang, Hebei 050017, China

摘要

摘要: 蛋白质二硫键异构酶(protein disulfide isomerase, PDI)是蛋白质二硫键异构酶家族的原型成员，由P4HB(prolyl 4-hydroxylase subunit beta)基因编码，是脯氨酸-4-羟化酶P4H蛋白的β亚基，故又称P4HB。主要存在于内质网中，通过酶活性和分子伴侣功能帮助蛋白质正确折叠，在病理生理进程中发挥重要作用。国内外对PDI的相关研究诸如癌症、神经退行性疾病等疾病中的作用机制进行了探讨，除了在内质网中的关键作用外，细胞表面PDI在启动血栓形成过程中的作用尤为突出。PDI可以迅速从血管损伤部位的活化血小板和内皮细胞中分泌出来，促进血小板活化和纤维蛋白形成，同时也能介导凝血因子活化、释放和凝血通路激活。用抗体或小分子抑制剂抑制PDI会阻止血栓形成。鉴于细胞外PDI在血栓调控中的重要作用，因此了解蛋白质二硫键异构酶血栓疾病致病机制势在必行。目前正在努力确定PDI的细胞外底物，这些底物参与了蛋白质二硫键异构酶与血栓形成之间的网络途径。本文重点阐述目前对蛋白质二硫键异构酶介导血栓形成机制的理解，并讨论通过靶向PDI阻断血栓形成的研究进展，以期为进一步探讨该物质防治血栓性疾病的应用提供新的思路。
- 蛋白质二硫键异构酶 /
- 血栓形成 /
- P4HB /
- 疾病致病机制
Abstract: Protein disulfide isomerase (PDI), the prototypical member of the PDI family, is encoded by the prolyl 4-hydroxylase subunit beta (P4HB) gene and is the β subunit of the P4H protein, so it is also called P4HB. It is mainly found in the endoplasmic reticulum (ER) and plays an important role in pathophysiological processes by promoting correct protein folding through enzymatic activity and molecular chaperone function. Related studies on PDI in China and abroad have explored the mechanisms of action in diseases, such as cancer and neurodegenerative diseases. In addition to its key role in ER, the role of cell surface PDI in initiating the thrombosis process is particularly prominent. PDI can be rapidly secreted from activated platelets and endothelial cells at the site of vascular injury to promote platelet activation and fibrin formation and mediate the activation of coagulation factor, its release and the coagulation pathway. Inhibition of PDI with antibodies or small-molecule inhibitors may prevent thrombosis. Given the important role of extracellular PDI in the regulation of thrombosis, scholars should aim to understand the pathogenic mechanism of PDI thrombotic disease. Efforts are ongoing to identify extracellular PDI substrates that participate in the network pathway between PDI and thrombosis. In this paper, we summarise our current understanding of the mechanism of PDI-mediated thrombosis, discusses the research progress in blocking thrombosis by targeted PDI and provide new ideas for further exploration of the application of this substance in the prevention and treatment of thrombotic diseases.
- Protein disulfide isomerase /
- Thrombosis /
- Prolyl 4-hydroxylase subunit beta /
- Pathogenesis of the disease

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图 1 PDI的结构域

Figure 1. Domain structure of PDI

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