Li Chenglong, Fei Chengshuo, Le Shiyong, Lai Zhongming, Yan Bo, Wang Liang, Zhang Zhongmin
Division of Spine Surgery, Department of Orthopedics, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Department of Orthopedics, The Third Affiliated Hospital, Southern Medical University, Academy of Orthopedics, Guangzhou, China.
Front Cell Dev Biol. 2024 Sep 16;12:1416345. doi: 10.3389/fcell.2024.1416345. eCollection 2024.
Ferroptosis plays a significant role in intervertebral disc degeneration (IDD). Understanding the key genes regulating ferroptosis in IDD could reveal fundamental mechanisms of the disease, potentially leading to new diagnostic and therapeutic targets.
Public datasets (GSE23130 and GSE70362) and the FerrDb database were analyzed to identify ferroptosis-related genes (DE-FRGs) involved in IDD. Single-cell RNA sequencing data (GSE199866) was used to validate the specific roles and expression patterns of these genes. Immunohistochemistry and Western blot analyses were subsequently conducted in both clinical samples and mouse models to assess protein expression levels across different tissues.
The analysis identified seven DE-FRGs, including , , , , , , and , with their expression patterns confirmed by single-cell RNA sequencing. Immunohistochemistry and Western blot analysis further revealed that , , , , , and exhibited differential expression during the progression of IDD. Additionally, the study highlighted the potential immune-modulatory functions of these genes within the IDD microenvironment.
Our study elucidates the critical role of ferroptosis in IDD and identifies specific genes, such as and , as potential targets for diagnosis and therapy. These findings offer new insights into the molecular mechanisms underlying IDD and present promising avenues for future research and clinical applications.
铁死亡在椎间盘退变（IDD）中起重要作用。了解调节IDD中铁死亡的关键基因可揭示该疾病的基本机制，有可能带来新的诊断和治疗靶点。
分析公共数据集（GSE23130和GSE70362）以及FerrDb数据库，以鉴定参与IDD的铁死亡相关基因（DE - FRGs）。使用单细胞RNA测序数据（GSE199866）验证这些基因的具体作用和表达模式。随后在临床样本和小鼠模型中进行免疫组织化学和蛋白质印迹分析，以评估不同组织中的蛋白质表达水平。
分析鉴定出7个DE - FRGs，包括[具体基因未列出]，其表达模式经单细胞RNA测序确认。免疫组织化学和蛋白质印迹分析进一步显示，[具体基因未列出]在IDD进展过程中表现出差异表达。此外，该研究突出了这些基因在IDD微环境中的潜在免疫调节功能。
我们的研究阐明了铁死亡在IDD中的关键作用，并鉴定出特定基因，如[具体基因未列出]，作为诊断和治疗的潜在靶点。这些发现为IDD潜在的分子机制提供了新见解，并为未来研究和临床应用提供了有前景的途径。
