Senescence in Intervertebral Disc Degeneration: A Comprehensive Analysis Based on Bioinformatic Strategies

IF 3.1 4区医学 Q3 IMMUNOLOGY

Immunity, Inflammation and Disease Pub Date : 2024-11-18 DOI:10.1002/iid3.70072

Zijun Zhao, Yining Wang, Zairan Wang, Fan Zhang, Ze Ding, Tao Fan

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引用次数: 0

Abstract

Background

Intervertebral disc degeneration (IDD) is a major cause for low back pain. Studies showed the association between senescence and degenerative diseases. Cell senescence can promote the occurrence and development of degenerative diseases through multiple mechanisms including inflammatory stress, oxidative stress and nutritional deprivation. The roles of senescence and senescence-associated genes (SAGs) remains unknown in IDD.

Methods

Four differently expressed SAGs were identified as hub SAGs using “limma“ package in R. We then calculated the immune infiltration of IDD patients, and investigated the relation between hub SAGs and immune infiltration. Enrichment analysis was performed to explore the functions of hub SAGs in IDD. Nomogram and LASSO model based on hub SAGs was constructed to predict the risk of severe degeneration (SD) for IDD patients. Subsequently, single cell analysis was conducted to describe the expression pattern of hub SAGs in intervertebral disc tissue.

Results

We identified ASPH, CCND1, IGFBP3 and SGK1 as hub SAGs. Further analysis demonstrated that the hub SAGs might mediate the development of IDD by regulating immune infiltration and multiple pathways. The LASSO model based on the four hub SAGs showed good performance in predicting the risk of SD. Single cell analysis revealed that ASPH, CCND1 and SGK1 mainly expressed in nucleus pulposus cells, while IGFBP3 mainly expressed in epithelial cells. Eleven candidate drugs targeting hub SAGS were predicted for IDD patients through Comparative Toxicogenomics Database (CDT). PCR and immunohistochemical analysis showed that the levels of four hub SAGs were higher in SD than MD (mild degeneration) patients.

Conclusions

We performed a comprehensive analysis of SAGs in IDD, which revealed their functions and expression pattern in intervertebral disc tissue. Based on hub SAGs, we established a predictive model and explored the potential drugs. These findings provide new understandings of SAG mechanism and promising therapeutic strategies for IDD.

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椎间盘退化中的衰老：基于生物信息学策略的综合分析

背景：椎间盘退变（IDD）是腰背痛的主要原因。研究表明，衰老与退行性疾病之间存在关联。细胞衰老可通过炎症应激、氧化应激和营养缺乏等多种机制促进退行性疾病的发生和发展。衰老和衰老相关基因（SAGs）在 IDD 中的作用仍然未知：然后我们计算了 IDD 患者的免疫浸润，并研究了中枢 SAG 与免疫浸润之间的关系。我们还进行了富集分析，以探索中枢 SAGs 在 IDD 中的功能。构建了基于枢纽SAGs的提名图和LASSO模型，以预测IDD患者发生严重变性（SD）的风险。随后，进行了单细胞分析以描述枢纽 SAGs 在椎间盘组织中的表达模式：结果：我们发现 ASPH、CCND1、IGFBP3 和 SGK1 是枢纽 SAGs。进一步分析表明，中枢 SAGs 可能通过调节免疫浸润和多种途径介导 IDD 的发生。基于四个中心 SAG 的 LASSO 模型在预测 SD 风险方面表现良好。单细胞分析显示，ASPH、CCND1和SGK1主要在髓核细胞中表达，而IGFBP3主要在上皮细胞中表达。通过比较毒物基因组学数据库（CDT），预测了11种针对IDD患者的枢纽SAGS候选药物。PCR和免疫组化分析表明，SD患者中4种中枢SAGs的水平高于MD（轻度变性）患者：我们对 IDD 中的 SAGs 进行了全面分析，揭示了它们在椎间盘组织中的功能和表达模式。基于枢纽 SAGs，我们建立了一个预测模型，并探索了潜在的药物。这些发现为 SAG 的作用机制和 IDD 的治疗策略提供了新的认识。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Immunity, Inflammation and Disease Medicine-Immunology and Allergy

CiteScore

3.60

自引率

0.00%

发文量

146

审稿时长

8 weeks

期刊介绍： Immunity, Inflammation and Disease is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research across the broad field of immunology. Immunity, Inflammation and Disease gives rapid consideration to papers in all areas of clinical and basic research. The journal is indexed in Medline and the Science Citation Index Expanded (part of Web of Science), among others. It welcomes original work that enhances the understanding of immunology in areas including: • cellular and molecular immunology • clinical immunology • allergy • immunochemistry • immunogenetics • immune signalling • immune development • imaging • mathematical modelling • autoimmunity • transplantation immunology • cancer immunology