自噬相关基因在骨性关节炎滑膜组织中的表达变化及调控作用机制研究

doi:10.3760/cma.j.cn441417-20250311-15009

国际医药卫生导报 ›› 2025, Vol. 31 ›› Issue (15): 2508-2514.DOI: 10.3760/cma.j.cn441417-20250311-15009

自噬相关基因在骨性关节炎滑膜组织中的表达变化及调控作用机制研究

董强¹ 余红超² 冯玮²

¹陕西省核工业二一五医院康复医学科，咸阳 712000；²陕西中医药大学附属医院骨伤医院康复病区，咸阳 712000

收稿日期:2025-03-11 出版日期:2025-08-01 发布日期:2025-08-21
通讯作者: 冯玮，Email：fengwei_67927@163.com
基金资助:
陕西省重点研发计划（2022SF-538）

Expression of autophagy-related genes in synovial tissues of patients with osteoarthritis and establishment of regulatory network

Dong Qiang¹, Yu Hongchao², Feng Wei²

¹Department of Rehabilitation Medicine, 215 Hospital of Shaanxi Nuclear Industry, Xianyang 712000, China; ²Department of Rehabilitation ward, Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine Orthopedic Hospital, Xianyang 712000, China

Received:2025-03-11 Online:2025-08-01 Published:2025-08-21
Contact: Feng Wei, Email:fengwei_67927@163.com
Supported by:
Key R & D Program of Shaanxi Province (2022SF-538)

摘要/Abstract

摘要：

目的　本研究采用基因组学和生物信息学方法分析自噬相关基因（ATGs）对骨性关节炎的潜在影响机制，为其防治提供参考依据。方法　检索获得2004年11月2日至2014年2月28日提交的公共数据集GSE55457、GSE55235、GSE1919，使用在线软件Network Analyst对数据预处理，然后进行差异表达基因（Log₂Fold Change>2，Adjusted P-value<0.05）的筛选，获取ATGs和OA的共同差异表达基因，用在线分析软件String进行生物学功能和信号通路的富集分析。采用Cytoscape 3.7.2建立蛋白-蛋白相互作用（PPI）网络、特异性ATGs的PPI网络、ATG-microRNA调控网络、转录因子（TF）-ATG调控网络、环境化学物-ATG调控网络。结果　ATGs在骨性关节炎中的基因表达模式发生明显改变，共发现106个骨性关节炎相关的差异表达的自噬相关基因列表（OA-AT-DEGs），其中上调43个（40.57%），下调63个（59.43%）；富集分析显示，ATGs主要参与对病毒相关的防御反应等生物学过程；OA-AT-DEGs和特异性的PPI网络显示，UBC、MAPK1和RPS6KB1为OA-AT-DEGs相关的PPI网络的重要核心节点。根据microRNA-OA-AT-DEGs交互作用网络显示，有21个microRNA与OA-AT-DEGs之间存在着调控作用。其中，hsa-miR-16-5P与8个OA-AT-DEGs存在靶向交互关系；表明BCL2、CDKN1A等相关基因受TF的调节；ATGs与环境化学物雌二醇、丙戊酸等有交互作用。结论　骨性关节炎患者的基因表达模式出现了显著改变，UBC和RPS6KB1等蛋白或基因可能在防御免疫机制中具有重要作用，microRNA、TF、环境化学物、信号通路分子、特异性基因在上述过程中具有相当作用，为研究ATGs对于骨性关节炎的影响和制定临床预防、诊断、治疗措施提供了新思路。

关键词:

骨性关节炎, 自噬相关基因, 基因表达, 文献分析

Abstract:

Objective　This study aims to analyze the potential mechanisms of autophagy-related genes (ATGs) in osteoarthritis using genomics and bioinformatics methods, providing a reference for its prevention and treatment. Methods　Public datasets GSE55457, GSE55235, and GSE1919 submitted between November 2, 2004, and February 28, 2014, were retrieved. Data preprocessing was conducted using the online software Network Analyst, followed by the selection of differentially expressed genes (Log₂Fold Change>2, Adjusted P-value<0.05) to identify common differentially expressed genes between ATGs and osteoarthritis. Biological function and pathway enrichment analysis were performed using the online analysis software String. Cytoscape 3.7.2 was employed to establish protein-protein interaction (PPI) networks, specific ATG PPI networks, ATG-microRNA regulatory networks, transcription factor (TF)-ATG regulatory networks, and environmental chemical-ATG regulatory networks. Results　ATGs in osteoarthritis (OA) showed significant changes, with a total of 106 differentially expressed autophagy-related genes identified (OA-AT-DEGs), including 43 upregulated (40.57%) and 63 downregulated (59.43%). Enrichment analysis indicated that ATGs are mainly involved in biological processes related to defense responses against viral infections. The OA-AT-DEGs and specific PPI networks revealed that UBC, MAPK1, and RPS6KB1 are important core nodes in the OA-AT-DEGs-related PPI network. The microRNA-OA-AT-DEGs interaction network showed that 21 microRNAs have regulatory interactions with OA-AT-DEGs. Among these, hsa-miR-16-5P has a targeting interaction with 8 OA-AT-DEGs, indicating that genes such as BCL2 and CDKN1A are regulated by TF. Additionally, ATGs interact with environmental chemicals such as estradiol and valproate. Conclusion　The gene expression pattern of patients with osteoarthritis has changed significantly, and proteins or genes such as UBC and RPS6KB1 may play an important role in the defense immune mechanism. Micro-RNA, TF, signaling pathway molecules, environmental chemicals and specific genes also play a role in the above process, providing new insights for studying the impact of autophagy genes on osteoarthritis and for developing clinical prevention, diagnosis, and treatment strategies.

Key words:

Osteoarthritis, Autophagy-related genes, Gene expression, Document analysis

董强余红超冯玮.

自噬相关基因在骨性关节炎滑膜组织中的表达变化及调控作用机制研究 [J]. 国际医药卫生导报, 2025, 31(15): 2508-2514.

Dong Qiang, Yu Hongchao, Feng Wei.

Expression of autophagy-related genes in synovial tissues of patients with osteoarthritis and establishment of regulatory network [J]. International Medicine and Health Guidance News, 2025, 31(15): 2508-2514.

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自噬相关基因在骨性关节炎滑膜组织中的表达变化及调控作用机制研究

Expression of autophagy-related genes in synovial tissues of patients with osteoarthritis and establishment of regulatory network

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