Li Jiyu, Jin Hui, Zhao Xinmin, Sun Xinran, Zhong Jiyuan, Zhao Jian, Yan Meijuan
Department of Orthopedic Oncology, Second Affiliated Hospital of Naval Medical University, Shanghai, China.
The Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, China.
Biomol Biomed. 2024 Dec 11;25(1):226-239. doi: 10.17305/bb.2024.11088.
Inflammation of the central nervous system (CNS) is a common feature of neurological disorders and infections, playing a crucial role in the development of CNS-related conditions. CNS inflammation is primarily regulated by glial cells, with astrocytes being the most abundant type in the mammalian CNS. Numerous studies have demonstrated that astrocytes, as immunocompetent cells, perform diverse and complex functions in both health and disease. Glycosylation, a critical post-translational modification of proteins, regulates numerous biological functions. The expression and activity of glycosyltransferases, the enzymes responsible for glycosylation, are closely associated with the pathogenesis of various diseases. β-1,4-GalTI, a mammalian glycosyltransferase, plays a significant role in cell-cell interactions, adhesion, and migration. Although many studies have focused on β-1,4-GalTI, few have explored its effects on astrocyte function. In this study, we constructed lentiviral vectors for both interference and overexpression of β-1,4-GalTI and discovered that β-1,4-GalTI knockdown inhibited astrocyte migration and proliferation, while its overexpression promoted these processes. Concurrently, β-1,4-GalTI knockdown reduced the expression of TNF-α, IL-1β, and IL-6, whereas overexpression enhanced the expression of these cytokines. These findings suggest that modulating β-1,4-GalTI activity can influence the molecular functions of astrocytes and provide a theoretical foundation for further research into β-1,4-GalTI as a potential therapeutic target in astrocyte-mediated inflammation.
中枢神经系统（CNS）炎症是神经疾病和感染的常见特征，在中枢神经系统相关病症的发展中起关键作用。中枢神经系统炎症主要由神经胶质细胞调节，星形胶质细胞是哺乳动物中枢神经系统中数量最多的类型。众多研究表明，星形胶质细胞作为具有免疫活性的细胞，在健康和疾病状态下均执行多样且复杂的功能。糖基化是蛋白质一种关键的翻译后修饰，可调节众多生物学功能。糖基转移酶（负责糖基化的酶）的表达和活性与多种疾病的发病机制密切相关。β-1,4-半乳糖基转移酶I（β-1,4-GalTI）是一种哺乳动物糖基转移酶，在细胞间相互作用、黏附和迁移中起重要作用。尽管许多研究聚焦于β-1,4-GalTI，但很少有研究探讨其对星形胶质细胞功能的影响。在本研究中，我们构建了用于干扰和过表达β-1,4-GalTI的慢病毒载体，发现敲低β-1,4-GalTI可抑制星形胶质细胞迁移和增殖，而过表达则促进这些过程。同时，敲低β-1,4-GalTI可降低肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和白细胞介素-6（IL-6）的表达，而过表达则增强这些细胞因子的表达。这些发现表明，调节β-1,4-GalTI活性可影响星形胶质细胞的分子功能，并为进一步研究β-1,4-GalTI作为星形胶质细胞介导炎症的潜在治疗靶点提供理论基础。
