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人龈沟液的蛋白质组学图谱揭示了牙周炎临床进展过程中的特定生物学和分子过程。

Proteomic profile of human gingival crevicular fluid reveals specific biological and molecular processes during clinical progression of periodontitis.

作者信息

Torres Alfredo, Michea M Angélica, Végvári Ákos, Arce Marion, Morales Alicia, Lanyon Elías, Alcota Marcela, Fuentes Camila, Vernal Rolando, Budini Mauricio, Zubarev Roman A, González Fermín E

机构信息

Laboratory of Experimental Immunology & Cancer, Faculty of Dentistry, University of Chile, Santiago, Chile.

Department of Conservative Dentistry, Faculty of Dentistry, University of Chile, Santiago, Chile.

出版信息

J Periodontal Res. 2023 Oct;58(5):1061-1081. doi: 10.1111/jre.13169. Epub 2023 Jul 31.

Abstract

BACKGROUND AND OBJECTIVE

There is no clear understanding of molecular events occurring in the periodontal microenvironment during clinical disease progression. Our aim was to explore qualitative and quantitative differences in gingival crevicular fluid (GCF) protein profiles from patients diagnosed with periodontitis between non-progressive and progressive periodontal sites.

METHODS

Five systemically healthy patients diagnosed with periodontitis were monitored weekly in their progression of the disease and GCF samples from 10 candidate sites were obtained. Two groups of five sites, matched from an equal number of teeth, were selected from the five patients: Progression (PG) and Non-Progression (NP). Global protein identification was performed with high-throughput proteomic approaches and label-free analysis determined their relative abundances. Proteins were identified by Proteome Discoverer v2.4 and searched against human SwissProt protein databases. Enrichment bioinformatic analyses were performed in STRING-DB and ShinyGO environment.

RESULTS

1504 and 1500 proteins were identified in NP and PG respectively. Forty-eight proteins were exclusively identified in PG, while 52 were identified in NP. Moreover, 35 proteins were more abundant in PG and 29 proteins in NP (twofold change, p < .05). The NP group was mainly represented by proteins from "response to biotic stimuli and other organisms," "processes of cell death regulation," "peptidase regulation," "protein ubiquitination," and "ribosomal activity" GO categories. The most represented GO categories of the PG group were "assembly of multiprotein complexes," "catabolic processes," "lipid metabolism," and "binding to hemoglobin and haptoglobin."

CONCLUSIONS

There are quantitative and qualitative differences in the proteome of GCF from periodontal sites according to the status of clinical progression of periodontitis. Progressive periodontitis sites are characterized by a protein profile associated with catabolic processes, immune response, and response to cellular stress, while stable periodontitis sites show a protein profile mainly related to wound repair and healing processes, cell death regulation, and chaperone-mediated autophagy. Understanding the etiopathogenic role of these profiles in progressive periodontitis may help to develop new diagnostic and therapeutic approaches.

摘要

背景与目的

目前对于临床疾病进展过程中牙周微环境中发生的分子事件尚无清晰的认识。我们的目的是探究在被诊断为牙周炎的患者中,非进展性和进展性牙周部位龈沟液(GCF)蛋白质谱的定性和定量差异。

方法

对5名全身健康且被诊断为牙周炎的患者的疾病进展情况进行每周监测,并从10个候选部位获取GCF样本。从这5名患者中选取两组各5个部位,这些部位来自相同数量的牙齿且相互匹配:进展组(PG)和非进展组(NP)。采用高通量蛋白质组学方法进行全局蛋白质鉴定,并通过无标记分析确定其相对丰度。通过Proteome Discoverer v2.4鉴定蛋白质,并在人类SwissProt蛋白质数据库中进行搜索。在STRING-DB和ShinyGO环境中进行富集生物信息学分析。

结果

在NP组和PG组中分别鉴定出1504种和1500种蛋白质。有48种蛋白质仅在PG组中被鉴定出,而52种在NP组中被鉴定出。此外,35种蛋白质在PG组中更为丰富,29种蛋白质在NP组中更为丰富(两倍变化,p < 0.05)。NP组主要由来自“对生物刺激和其他生物体的反应”“细胞死亡调控过程”“肽酶调控”“蛋白质泛素化”和“核糖体活性”等基因本体(GO)类别的蛋白质组成。PG组中最具代表性的GO类别是“多蛋白复合物组装”“分解代谢过程”“脂质代谢”以及“与血红蛋白和触珠蛋白结合”。

结论

根据牙周炎临床进展状态,牙周部位GCF的蛋白质组存在定量和定性差异。进展性牙周炎部位的蛋白质谱特征与分解代谢过程、免疫反应以及细胞应激反应相关,而稳定型牙周炎部位的蛋白质谱主要与伤口修复和愈合过程、细胞死亡调控以及伴侣介导的自噬有关。了解这些蛋白质谱在进展性牙周炎中的致病作用可能有助于开发新的诊断和治疗方法。

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