中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (5): 969-975.doi: 10.4103/1673-5374.355744

• 综述:退行性病与再生 • 上一篇    下一篇

波形蛋白作为多种神经系统疾病的潜在干预靶点

  

  • 出版日期:2023-05-15 发布日期:2022-11-01
  • 基金资助:
    国家自然科学基金(82071374);广东医科大学学科建设项目(1.13和4.1.19);广东医科大学大学生创新实验项目(FYDB015、ZCDS001、ZYDB004、ZYDB016和ZZDI001); 大学生科技创新培训项目(GDMU2020194,GDMU2020195,GDMU2021021,GDMU2021023,GDMU2021091,GDMU2021111)

Vimentin as a potential target for diverse nervous system diseases

Kang-Zhen Chen1, 2, #, Shu-Xian Liu1, #, Yan-Wei Li1, #, Tao He2, Jie Zhao2, Tao Wang3, *, Xian-Xiu Qiu2, *, Hong-Fu Wu1, 2, *   

  1. 1Department of Anesthesiology, Guangzhou Huadu Hospital Affiliated to Guangdong Medical University (Guangzhou Huadu District Maternal and Child Health Care Hospital), Guangzhou, Guangdong Province, China;  2Dongguan City Key Laboratory of Stem Cell and Regenerative Tissue Engineering, Guangdong Medical University, Dongguan, Guangdong Province, China;  3Department of Surgery, the Third Hospital of Guangdong Medical University (Longjiang Hospital of Shunde District), Foshan, Guangdong Province, China 
  • Online:2023-05-15 Published:2022-11-01
  • Contact: Hong-Fu Wu, PhD, hongfuw@126.com; Xian-Xiu Qiu, PhD, bmsqiu@gdmu.edu.cn; Tao Wang, PhD, job1982@126.com.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, No. 82071374; Discipline Construction Project of Guangdong Medical University, Nos. 1.13 and 4.1.19; College Students Innovative Experimental Project in Guangdong Medical University, Nos. FYDB015, ZCDS001, ZYDB004, ZYDB016, and ZZDI001; and College Students’ Science and Technology Innovation Training Project, Nos. GDMU2020194, GDMU2020195, GDMU2021021, GDMU2021023, GDMU2021091, GDMU2021111 (all to HFW).

摘要:

波形蛋白是一种主要的Ⅲ型中间丝蛋白,在细胞迁移、增殖和分裂等几种基本细胞功能中发挥重要作用。虽然波形蛋白是一种细胞质蛋白,但它也存在于细胞外基质和细胞表面。既往研究表明,波形蛋白可以在不同的神经系统损伤和疾病中可发挥多种生理作用。例如,波形蛋白在脊髓损伤和脑卒中的研究主要集中于反应性星形胶质细胞的形成上。脊髓损伤后,波形蛋白和胶质纤维酸性蛋白敲除(GFAP-/-VIM-/-)小鼠,神经胶质瘢痕明显减少,伴随着轴突再生和运动功能改善。然而,GFAP-/-VIM-/-小鼠在脑卒中后胶质瘢痕减少则导致神经元网络异常恢复和较差的神经功能恢复。事实上,相反的结果归因于胶质瘢痕在不同时间和空间条件下的多重作用。此外,细胞外波形蛋白可能是一种新的神经营养因子,能够通过与胰岛素样生长因子1受体相互作用来促进轴突延伸。在细菌性脑膜炎的发病机制中,细胞表面波形蛋白是多种致病菌(大肠杆菌K1,单核细胞增多性李斯特菌和B族链球菌)的结合受体,促进脑膜炎发生发展,与野生型小鼠相比,VIM-/-小鼠对细菌感染的敏感性较低,炎症反应较少,这表明波形蛋白是诱导脑膜炎发生的关键。分析最近发表的文献,发现波形蛋白是神经系统中的一把双刃剑,参与调节轴突再生、髓鞘形成、细胞凋亡和神经炎症等多种过程。本综述系统地讨论了波形蛋白在脊髓损伤、脑卒中、细菌性脑膜炎、胶质瘤和周围神经损伤中的应用,及调控波形蛋白在改善轴突再生、减少感染、抑制脑肿瘤进展和增强神经髓鞘化等多方面的潜在治疗方法。

https://orcid.org/0000-0002-1115-3681 (Hong-Fu Wu); 

https://orcid.org/0000-0003-3218-2331 (Xian-Xiu Qiu); 

https://orcid.org/0000-0002-4189-7155 (Tao Wang)

关键词: 星形胶质细胞, 轴突再生, 细菌性脑膜炎, 胶质疤痕, 胶质瘤, 神经系统疾病, 周围神经系统损伤, 脊髓损伤, 脑卒中, 波形蛋白

Abstract: Vimentin is a major type III intermediate filament protein that plays important roles in several basic cellular functions including cell migration, proliferation, and division. Although vimentin is a cytoplasmic protein, it also exists in the extracellular matrix and at the cell surface. Previous studies have shown that vimentin may exert multiple physiological effects in different nervous system injuries and diseases. For example, the studies of vimentin in spinal cord injury and stroke mainly focus on the formation of reactive astrocytes. Reduced glial scar, increased axonal regeneration, and improved motor function have been noted after spinal cord injury in vimentin and glial fibrillary acidic protein knockout (GFAP–/–VIM–/–) mice. However, attenuated glial scar formation in post-stroke in GFAP–/– VIM–/– mice resulted in abnormal neuronal network restoration and worse neurological recovery. These opposite results have been attributed to the multiple roles of glial scar in different temporal and spatial conditions. In addition, extracellular vimentin may be a neurotrophic factor that promotes axonal extension by interaction with the insulin-like growth factor 1 receptor. In the pathogenesis of bacterial meningitis, cell surface vimentin is a meningitis facilitator, acting as a receptor of multiple pathogenic bacteria, including E. coli K1, Listeria monocytogenes, and group B streptococcus. Compared with wild type mice, VIM–/– mice are less susceptible to bacterial infection and exhibit a reduced inflammatory response, suggesting that vimentin is necessary to induce the pathogenesis of meningitis. Recently published literature showed that vimentin serves as a double-edged sword in the nervous system, regulating axonal regrowth, myelination, apoptosis, and neuroinflammation. This review aims to provide an overview of vimentin in spinal cord injury, stroke, bacterial meningitis, gliomas, and peripheral nerve injury and to discuss the potential therapeutic methods involving vimentin manipulation in improving axonal regeneration, alleviating infection, inhibiting brain tumor progression, and enhancing nerve myelination.

Key words: astrocytes, axonal regeneration, bacterial meningitis, glial scar, gliomas, nervous system diseases, peripheral nervous system injury, spinal cord injury, stroke, vimentin