Jinan Central Hospital, Shandong University, Jinan, Shandong, China.
Central Hospital Affiliated to Shandong First Medical University, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China.
Aging Dis. 2024 Feb 1;15(1):153-168. doi: 10.14336/AD.2023.0512.
Reactive astrocytes (RAs) produce chondroitin sulfate proteoglycans (CSPGs) in large quantities after spinal cord injury (SCI) and inhibit axon regeneration through the Rho-associated protein kinase (ROCK) pathway. However, the mechanism of producing CSPGs by RAs and their roles in other aspects are often overlooked. In recent years, novel generation mechanisms and functions of CSPGs have gradually emerged. Extracellular traps (ETs), a new recently discovered phenomenon in SCI, can promote secondary injury. ETs are released by neutrophils and microglia, which activate astrocytes to produce CSPGs after SCI. CSPGs inhibit axon regeneration and play an important role in regulating inflammation as well as cell migration and differentiation; some of these regulations are beneficial. The current review summarized the process of ET-activated RAs to generate CSPGs at the cellular signaling pathway level. Moreover, the roles of CSPGs in inhibiting axon regeneration, regulating inflammation, and regulating cell migration and differentiation were discussed. Finally, based on the above process, novel potential therapeutic targets were proposed to eliminate the adverse effects of CSPGs.
反应性星形胶质细胞（RAs）在脊髓损伤（SCI）后大量产生硫酸软骨素蛋白聚糖（CSPGs），并通过 Rho 相关蛋白激酶（ROCK）通路抑制轴突再生。然而，RAs 产生 CSPGs 的机制及其在其他方面的作用往往被忽视。近年来，CSPGs 的新型产生机制和功能逐渐显现。细胞外陷阱（ETs）是 SCI 中最近发现的一种新现象，可促进二次损伤。ETs 由中性粒细胞和小胶质细胞释放，SCI 后激活星形胶质细胞产生 CSPGs。CSPGs 抑制轴突再生，并在调节炎症以及细胞迁移和分化方面发挥重要作用；其中一些调节作用是有益的。本综述总结了 ET 激活的 RAs 在细胞信号通路水平产生 CSPGs 的过程。此外，还讨论了 CSPGs 在抑制轴突再生、调节炎症以及调节细胞迁移和分化中的作用。最后，基于上述过程，提出了新的潜在治疗靶点，以消除 CSPGs 的不良影响。
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