Ginsenoside Rg1 Regulates Immune Microenvironment and Neurological Recovery After Spinal Cord Injury Through MYCBP2 Delivery via Neuronal Cell-Derived Extracellular Vesicles

被引：5

作者：

Rong, Yuluo ^{[1
,2
]}

Wang, Jiaxing ^{[3
]}

Hu, Tao ^{[1
]}

Shi, Zhongming ^{[1
]}

Lang, Chuandong ^{[1
]}

Liu, Wei ^{[4
]}

Cai, Weihua ^{[3
]}

Sun, Yongjin ^{[1
]}

Zhang, Feng ^{[1
]}

Zhang, Wenzhi ^{[1
]}

机构：

[1] Univ Sci & Technol China, Affiliated Hosp USTC 1, Div Life Sci & Med, Dept Orthopaed,Ctr Leading Med & Adv Technol IHM, Hefei 230001, Anhui, Peoples R China

[2] Shanghai Univ, Natl Ctr Translat Med Shanghai SHU Branch, Shanghai 200444, Peoples R China

[3] Nanjing Med Univ, Affiliated Hosp 1, Dept Orthoped, Nanjing 210029, Jiangsu, Peoples R China

[4] Naval Med Univ, Affiliated Hosp 2, Dept Orthoped, Shanghai 200003, Peoples R China

来源：

ADVANCED SCIENCE | 2024年

关键词：

extracellular vesicles; ginsenoside Rg1; microglial polarization; oxidative stress; spinal cord injury; OXIDATIVE STRESS; UBIQUITIN LIGASE; REPAIR; POLARIZATION; REGENERATION; EXOSOMES;

D O I：

10.1002/advs.202402114

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Spinal cord injury (SCI) is a severe neurological condition that frequently leads to significant sensory, motor, and autonomic dysfunction. This study sought to delineate the potential mechanistic underpinnings of extracellular vesicles (EVs) derived from ginsenoside Rg1-pretreated neuronal cells (Rg1-EVs) in ameliorating SCI. These results demonstrated that treatment with Rg1-EVs substantially improved motor function in spinal cord-injured mice. Rg1-EVs enhance microglial polarization toward the M2 phenotype and repressed oxidative stress, thereby altering immune responses and decreasing inflammatory cytokine secretion. Moreover, Rg1-EVs substantially diminish reactive oxygen species accumulation and enhanced neural tissue repair by regulating mitochondrial function. Proteomic profiling highlighted a significant enrichment of MYCBP2 in Rg1-EVs, and functional assays confirmed that MYCBP2 knockdown counteracted the beneficial effects of Rg1-EVs in vitro and in vivo. Mechanistically, MYCBP2 is implicated in the ubiquitination and degradation of S100A9, thereby promoting microglial M2-phenotype polarization and reducing oxidative stress. Overall, these findings substantiated the pivotal role of Rg1-EVs in neuronal protection and functional recovery following SCI through MYCBP2-mediated ubiquitination of S100A9. This research offers novel mechanistic insights into therapeutic strategies against SCI and supports the clinical potential of Rg1-EVs. The study reveals the potential mechanism by which extracellular vesicles (EVs) derived from ginsenoside Rg1-pretreated neuronal cells (Rg1-EVs) promote functional recovery after spinal cord injury. These findings demonstrate that Rg1-EVs enhance motor function recovery in mice by enhancing microglia's polarization toward the M2 phenotype and reducing oxidative stress, driven by MYCBP2-mediated ubiquitination and degradation of S100A9. image

引用

页数：18

共 51 条

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