Identification and Analysis of Mitochondria-Related Proteins in Haemophilic Arthritis Synovial Membranes Based on Proteomic Analysis

IF 3 2区医学 Q2 HEMATOLOGY

Haemophilia Pub Date : 2025-08-08 DOI:10.1111/hae.70110

Haitao Ma, Jiaxiang Zhang, Yongjie Yang, Liyin Liu, Defu Yu, Dasheng Luo, Tao Chen

{"title":"Identification and Analysis of Mitochondria-Related Proteins in Haemophilic Arthritis Synovial Membranes Based on Proteomic Analysis","authors":"Haitao Ma, Jiaxiang Zhang, Yongjie Yang, Liyin Liu, Defu Yu, Dasheng Luo, Tao Chen","doi":"10.1111/hae.70110","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>Haemophilic arthritis (HA), a severe complication in haemophiliacs, is driven by recurrent joint bleeding and iron overload from haemosiderin deposition, leading to synovial damage and joint dysfunction. Previous studies have examined the effects of iron overload on mitochondrial function, but the mechanisms linking iron metabolism disorders to mitochondrial dysfunction in HA remain poorly understood.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Comparative analyses of synovial samples from patients with advanced HA and osteoarthritis (OA) were performed using a proteomic approach. Differentially Expressed Proteins (DEPs) linked to mitochondrial function were identified and analysed for gene ontology (GO) and KEGG enrichment. A protein-protein interaction (PPI) network was constructed and findings were validated using Western blotting and Immunohistochemistry (IHC).</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>A total of 152 mitochondria-associated DEPs were identified, significantly enriched in processes such as oxidative phosphorylation, aerobic respiration and the TCA cycle. KEGG analysis revealed disruption of pathways including oxidative phosphorylation and fatty acid metabolism, highlighting metabolic dysregulation in advanced HA synovium. TEM analysis revealed mitochondrial abnormalities including swelling, cristae breaks and iron deposition. NDUFS1 and SOD2 were significantly down-regulated in advanced HA synovium, linked to reduce mitochondrial efficiency and enhanced oxidative stress.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>This study identifies molecular pathways and proteins linked to mitochondrial dysfunction in advanced HA, including those involved in the TCA cycle, oxidative phosphorylation and oxidative stress responses. The reduction in NDUFS1 and SOD2 expression may be correlated with mitochondrial dysfunction caused by iron overload in synovial fibroblasts. They provide new insights into the pathogenesis of late-stage HA and offer potential avenues for mitochondria-targeted therapeutic strategies.</p>\n </section>\n </div>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":"31 5","pages":"1066-1076"},"PeriodicalIF":3.0000,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Haemophilia","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/hae.70110","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"HEMATOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background

Haemophilic arthritis (HA), a severe complication in haemophiliacs, is driven by recurrent joint bleeding and iron overload from haemosiderin deposition, leading to synovial damage and joint dysfunction. Previous studies have examined the effects of iron overload on mitochondrial function, but the mechanisms linking iron metabolism disorders to mitochondrial dysfunction in HA remain poorly understood.

Methods

Comparative analyses of synovial samples from patients with advanced HA and osteoarthritis (OA) were performed using a proteomic approach. Differentially Expressed Proteins (DEPs) linked to mitochondrial function were identified and analysed for gene ontology (GO) and KEGG enrichment. A protein-protein interaction (PPI) network was constructed and findings were validated using Western blotting and Immunohistochemistry (IHC).

Results

A total of 152 mitochondria-associated DEPs were identified, significantly enriched in processes such as oxidative phosphorylation, aerobic respiration and the TCA cycle. KEGG analysis revealed disruption of pathways including oxidative phosphorylation and fatty acid metabolism, highlighting metabolic dysregulation in advanced HA synovium. TEM analysis revealed mitochondrial abnormalities including swelling, cristae breaks and iron deposition. NDUFS1 and SOD2 were significantly down-regulated in advanced HA synovium, linked to reduce mitochondrial efficiency and enhanced oxidative stress.

Conclusion

This study identifies molecular pathways and proteins linked to mitochondrial dysfunction in advanced HA, including those involved in the TCA cycle, oxidative phosphorylation and oxidative stress responses. The reduction in NDUFS1 and SOD2 expression may be correlated with mitochondrial dysfunction caused by iron overload in synovial fibroblasts. They provide new insights into the pathogenesis of late-stage HA and offer potential avenues for mitochondria-targeted therapeutic strategies.

Abstract Image

查看原文本刊更多论文

基于蛋白质组学分析的血友病关节炎滑膜线粒体相关蛋白的鉴定和分析。

背景：血友病关节炎（Haemophilic arthritis， HA）是血友病患者的一种严重并发症，由反复的关节出血和血黄素沉积引起的铁超载驱动，导致滑膜损伤和关节功能障碍。先前的研究已经检查了铁超载对线粒体功能的影响，但在血凝素中，铁代谢紊乱与线粒体功能障碍之间的联系机制仍然知之甚少。方法：采用蛋白质组学方法对晚期HA和骨关节炎（OA）患者的滑膜样本进行比较分析。鉴定并分析了与线粒体功能相关的差异表达蛋白（DEPs）的基因本体（GO）和KEGG富集。构建了蛋白-蛋白相互作用（PPI）网络，并利用Western blotting和免疫组化（IHC）对结果进行了验证。结果：共鉴定出152个线粒体相关的dep，在氧化磷酸化、有氧呼吸和TCA循环等过程中显著富集。KEGG分析揭示了氧化磷酸化和脂肪酸代谢等途径的破坏，突出了晚期HA滑膜的代谢失调。TEM分析显示线粒体异常，包括肿胀、嵴断裂和铁沉积。NDUFS1和SOD2在HA晚期滑膜中显著下调，与线粒体效率降低和氧化应激增强有关。结论：本研究确定了与晚期HA线粒体功能障碍相关的分子途径和蛋白质，包括参与TCA循环、氧化磷酸化和氧化应激反应的分子途径和蛋白质。NDUFS1和SOD2表达的减少可能与滑膜成纤维细胞铁超载引起的线粒体功能障碍有关。它们为晚期HA的发病机制提供了新的见解，并为线粒体靶向治疗策略提供了潜在的途径。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Haemophilia 医学-血液学

CiteScore

6.50

自引率

28.20%

发文量

226

审稿时长

3-6 weeks

期刊介绍： Haemophilia is an international journal dedicated to the exchange of information regarding the comprehensive care of haemophilia. The Journal contains review articles, original scientific papers and case reports related to haemophilia care, with frequent supplements. Subjects covered include: clotting factor deficiencies, both inherited and acquired: haemophilia A, B, von Willebrand''s disease, deficiencies of factor V, VII, X and XI replacement therapy for clotting factor deficiencies component therapy in the developing world transfusion transmitted disease haemophilia care and paediatrics, orthopaedics, gynaecology and obstetrics nursing laboratory diagnosis carrier detection psycho-social concerns economic issues audit inherited platelet disorders.