Li Yang
Orthopedics and Traumatology Department 3 (Spine), Changsha Hospital of Traditional Chinese Medicine Tianxin Campus, No.542, Shuyuan Road, Tianxin District, Changsha City, 410002, Hunan Province, China.
J Orthop Surg Res. 2025 May 26;20(1):517. doi: 10.1186/s13018-025-05922-w.
Spinal cord injury (SCI) is a neurological disorder characterized by severe and often irreversible damage to the spinal cord, for which no effective treatments currently exist. Ubiquitination, a reversible post-translational modification, plays a critical role in regulating protein degradation and stabilization. Tripartite motif-containing 55 (TRIM55), an E3 ubiquitin ligase, belongs to the TRIM protein family. This study aimed to explore the potential mechanism of TRIM55 in SCI.
An SCI rat model was established to investigate the effects of TRIM55 on SCI. LPS-stimulated PC12 cells were used to evaluate inflammation by measuring IL-1β, IL-6, and TNF-α levels using enzyme-linked immunosorbent assays. The proliferation and apoptosis of PC12 cells were assessed using the cell counting kit-8 assay and TUNEL staining. Quantitative real-time PCR, western blot analysis, co-immunoprecipitation, and cycloheximide chase experiments were performed to elucidate the underlying mechanism.
The findings revealed that TRIM55 was downregulated both in vitro and in vivo. Functionally, TRIM55 inhibited apoptosis and reduced the expression of pro-inflammatory cytokines in LPS-stimulated PC12 cells. Mechanistically, TRIM55 interacted with toll-like receptor 4 (TLR4) and promoted its degradation by modulating the ubiquitination process, thereby attenuating the inflammatory response. Furthermore, TRIM55 enhanced recovery from SCI and alleviated inflammation in vivo.
This study not only provides robust theoretical evidence supporting TRIM55 as an anti-inflammatory factor but also offers a novel therapeutic approach for SCI research.
脊髓损伤（SCI）是一种神经疾病，其特征是脊髓严重受损且往往不可逆转，目前尚无有效的治疗方法。泛素化是一种可逆的翻译后修饰，在调节蛋白质降解和稳定性方面起着关键作用。含三联基序蛋白55（TRIM55）是一种E3泛素连接酶，属于TRIM蛋白家族。本研究旨在探讨TRIM55在脊髓损伤中的潜在机制。
建立脊髓损伤大鼠模型以研究TRIM55对脊髓损伤的影响。使用脂多糖（LPS）刺激的PC12细胞，通过酶联免疫吸附测定法测量白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）水平来评估炎症。使用细胞计数试剂盒-8检测法和TUNEL染色评估PC12细胞的增殖和凋亡。进行定量实时聚合酶链反应、蛋白质免疫印迹分析、免疫共沉淀和放线菌酮追踪实验以阐明潜在机制。
研究结果显示，TRIM55在体外和体内均下调。在功能上，TRIM55抑制LPS刺激的PC12细胞凋亡并降低促炎细胞因子的表达。机制上，TRIM55与Toll样受体4（TLR4）相互作用，并通过调节泛素化过程促进其降解，从而减轻炎症反应。此外，TRIM55可促进脊髓损伤后的恢复并减轻体内炎症。
本研究不仅提供了有力的理论证据支持TRIM55作为一种抗炎因子，还为脊髓损伤研究提供了一种新的治疗方法。
