对人类牙龈缝隙液的多平台分析揭示了牙周炎临床进展过程中的一种相关调控细胞死亡机制--铁突变

IF 10.8 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE International Journal of Oral Science Pub Date : 2024-05-27 DOI:10.1038/s41368-024-00306-y
Alfredo Torres, M. Angélica Michea, Ákos Végvári, Marion Arce, Valentina Pérez, Marcela Alcota, Alicia Morales, Rolando Vernal, Mauricio Budini, Roman A. Zubarev, Fermín E. González
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引用次数: 0

摘要

铁蛋白沉积与许多慢性炎症性疾病的发病机制有关,但它与进展性牙周炎的关系仍未得到探讨。为了研究铁蛋白沉积在牙周炎进展过程中的参与和意义,我们对 16 名牙周炎确诊患者进行了评估。在十二周的时间里,我们通过每周一次的临床评估对患者的病情进展进行临床监测,并收集牙龈缝隙液(GCF)进行进一步分析。临床指标、蛋白质组数据、硅学方法和生物信息学工具相结合,确定了与牙周炎进展相关的蛋白质特征,并探索了它们与铁沉积的潜在联系。随后的 Western 印迹分析验证了主要发现。最后,分析了牙龈组织的单细胞 RNA 测序(scRNA-seq)数据集(GSE164241),以阐明牙周炎进展过程中的细胞动态。研究发现,牙周炎进展的速度比传统观点认为的要快。来自进展期和非进展期牙周部位的 GCF 样本显示出不同数量和质量的蛋白质组特征。此外,研究还揭示了进展期牙周炎的特定生物过程和分子功能,包括 SNCA、CA1、HBB、SLC4A1 和 ANK1 在内的一组枢纽蛋白与牙周炎的临床进展状态密切相关。此外,我们还发现了与铁突变相关的特定蛋白--驱动蛋白或抑制蛋白(SNCA、FTH1、HSPB1、CD44 和 GCLC),揭示了在牙周炎的临床进展过程中,这种特定类型的调控细胞死亡同时存在。此外,定量蛋白质组数据与 scRNA-seq 分析的整合表明,成纤维细胞易受铁变态反应的影响。我们的分析首次揭示了牙周病患者体内与铁变性有关的蛋白质和过程,为研究牙周病进展的分子机制提供了新的视角。这些发现可能会带来新的诊断和治疗策略。
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A multi-platform analysis of human gingival crevicular fluid reveals ferroptosis as a relevant regulated cell death mechanism during the clinical progression of periodontitis

Ferroptosis is implicated in the pathogenesis of numerous chronic-inflammatory diseases, yet its association with progressive periodontitis remains unexplored. To investigate the involvement and significance of ferroptosis in periodontitis progression, we assessed sixteen periodontitis-diagnosed patients. Disease progression was clinically monitored over twelve weeks via weekly clinical evaluations and gingival crevicular fluid (GCF) collection was performed for further analyses. Clinical metrics, proteomic data, in silico methods, and bioinformatics tools were combined to identify protein profiles linked to periodontitis progression and to explore their potential connection with ferroptosis. Subsequent western blot analyses validated key findings. Finally, a single-cell RNA sequencing (scRNA-seq) dataset (GSE164241) for gingival tissues was analyzed to elucidate cellular dynamics during periodontitis progression. Periodontitis progression was identified as occurring at a faster rate than traditionally thought. GCF samples from progressing and non-progressing periodontal sites showed quantitative and qualitatively distinct proteomic profiles. In addition, specific biological processes and molecular functions during progressive periodontitis were revealed and a set of hub proteins, including SNCA, CA1, HBB, SLC4A1, and ANK1 was strongly associated with the clinical progression status of periodontitis. Moreover, we found specific proteins - drivers or suppressors - associated with ferroptosis (SNCA, FTH1, HSPB1, CD44, and GCLC), revealing the co-occurrence of this specific type of regulated cell death during the clinical progression of periodontitis. Additionally, the integration of quantitative proteomic data with scRNA-seq analysis suggested the susceptibility of fibroblasts to ferroptosis. Our analyses reveal proteins and processes linked to ferroptosis for the first time in periodontal patients, which offer new insights into the molecular mechanisms of progressive periodontal disease. These findings may lead to novel diagnostic and therapeutic strategies.

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来源期刊
International Journal of Oral Science
International Journal of Oral Science DENTISTRY, ORAL SURGERY & MEDICINE-
CiteScore
31.80
自引率
1.30%
发文量
53
审稿时长
>12 weeks
期刊介绍: The International Journal of Oral Science covers various aspects of oral science and interdisciplinary fields, encompassing basic, applied, and clinical research. Topics include, but are not limited to: Oral microbiology Oral and maxillofacial oncology Cariology Oral inflammation and infection Dental stem cells and regenerative medicine Craniofacial surgery Dental material Oral biomechanics Oral, dental, and maxillofacial genetic and developmental diseases Craniofacial bone research Craniofacial-related biomaterials Temporomandibular joint disorder and osteoarthritis The journal publishes peer-reviewed Articles presenting new research results and Review Articles offering concise summaries of specific areas in oral science.
期刊最新文献
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