Department of Orthopedics, Shanghai Changzheng Hospital, Naval Medical University, Shanghai 200003, China.
Mediators Inflamm. 2023 Apr 8;2023:1164147. doi: 10.1155/2023/1164147. eCollection 2023.
Lumbar spinal stenosis (LSS), which can lead to irreversible neurologic damage and functional disability, is characterized by hypertrophy and fibrosis in the ligamentum flavum (LF). However, the underlying mechanism is still unclear. In the current study, the effect of Smurf1, a kind of E3 ubiquitin ligase, in promoting the fibrosis and oxidative stress of LF was investigated, and its underlying mechanism was explored. The expression of oxidative stress and fibrosis-related markers was assessed in the tissue of lumbar spinal stenosis (LSS) and lumbar disc herniation (LDH). Next, the expression of the top 10 E3 ubiquitin ligases, obtained from Gene Expression Omnibus (GEO) dataset GSE113212, was assessed in LDH and LSS, and confirmed that Smurf1 expression was markedly upregulated in the LSS group. Furthermore, Smurf1 overexpression promotes the fibrosis and oxidative stress of LF cells. Subsequently, NRF2, an important transcription factor for oxidative stress and fibrosis, was predicted to be a target of Smurf1. Mechanistically, Smurf1 directly interacts with Nrf2 and accelerates Nrf2 ubiquitination and degradation. In conclusion, the current study suggests that Smurf1 facilitated the fibrosis and oxidative stress of LF and induced the development of LSS by promoting Nrf2 ubiquitination and degradation.
腰椎管狭窄症（LSS）可导致不可逆的神经损伤和功能障碍，其特征是黄韧带（LF）的肥大和纤维化。然而，其潜在机制尚不清楚。在本研究中，研究了 E3 泛素连接酶 Smurf1 促进 LF 纤维化和氧化应激的作用，并探讨了其潜在机制。评估了腰椎管狭窄症（LSS）和腰椎间盘突出症（LDH）组织中氧化应激和纤维化相关标志物的表达。接下来，从基因表达综合数据库（GEO）数据集 GSE113212 中评估了前 10 种 E3 泛素连接酶的表达，并证实 Smurf1 在 LSS 组中的表达明显上调。此外，Smurf1 的过表达促进 LF 细胞的纤维化和氧化应激。随后，预测氧化应激和纤维化的重要转录因子 NRF2 是 Smurf1 的靶标。在机制上，Smurf1 直接与 Nrf2 相互作用，加速 Nrf2 的泛素化和降解。总之，本研究表明 Smurf1 通过促进 Nrf2 的泛素化和降解，促进 LF 的纤维化和氧化应激，从而诱导 LSS 的发生。
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