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慢性鼻-鼻窦炎和鼻息肉患者鼻分泌物的深度蛋白质组学分析

In-Depth, Proteomic Analysis of Nasal Secretions from Patients With Chronic Rhinosinusitis and Nasal Polyps.

作者信息

Kim Yi Sook, Han Dohyun, Kim JinYoup, Kim Dae Woo, Kim Yong Min, Mo Ji Hun, Choi Hyo Geun, Park Jong Wan, Shin Hyun Woo

机构信息

Obstructive Upper airway Research (OUaR) Laboratory, Department of Pharmacology, Seoul National University College of Medicine, Seoul, Korea.

Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea.

出版信息

Allergy Asthma Immunol Res. 2019 Sep;11(5):691-708. doi: 10.4168/aair.2019.11.5.691.

Abstract

PURPOSE

Chronic rhinosinusitis (CRS) is a complex immunological condition, and novel experimental modalities are required to explore various clinical and pathophysiological endotypes; mere evaluation of nasal polyp (NP) status is inadequate. Therefore, we collected patient nasal secretions on filter paper and characterized the proteomes.

METHODS

We performed liquid chromatography-mass spectrometry (MS)/MS in the data-dependent acquisition (DDA) and data-independent acquisition (DIA) modes. Nasal secretions were collected from 10 controls, 10 CRS without NPs (CRSsNP) and 10 CRS with NPs (CRSwNP). We performed Orbitrap MS-based proteomic analysis in the DDA (5 controls, 5 CRSsNP and 5 CRSwNP) and the DIA (5 controls, 5 CRSsNP and 5 CRSwNP) modes, followed by a statistical analysis and a hierarchical clustering to identify differentially expressed proteins in the 3 groups.

RESULTS

We identified 2,020 proteins in nasal secretions. Canonical pathway analysis and gene ontology (GO) evaluation revealed that interleukin (IL)-7, IL-9, IL-17A and IL-22 signaling and neutrophil-mediated immune responses like neutrophil degranulation and activation were significantly increased in CRSwNP compared to control. The GO terms related to the iron ion metabolism that may be associated with CRS and NP development.

CONCLUSIONS

Collection of nasal secretions on the filter paper is a practical and non-invasive method for in-depth study of nasal proteomics. Our proteomic signatures also support that Asian NPs could be characterized as non-eosinophilic inflammation features. Therefore, the proteomic profiling of nasal secretions from CRS patients may enhance our understanding of CRS endotypes.

摘要

目的

慢性鼻-鼻窦炎(CRS)是一种复杂的免疫性疾病,需要新的实验方法来探索各种临床和病理生理亚型;仅评估鼻息肉(NP)状态是不够的。因此,我们收集了患者滤纸上的鼻分泌物并对蛋白质组进行了表征。

方法

我们以数据依赖型采集(DDA)和数据非依赖型采集(DIA)模式进行液相色谱-质谱(MS)/MS分析。从10名对照、10名无NP的CRS(CRSsNP)患者和10名有NP的CRS(CRSwNP)患者中收集鼻分泌物。我们以DDA模式(5名对照、5名CRSsNP患者和5名CRSwNP患者)和DIA模式(5名对照、5名CRSsNP患者和5名CRSwNP患者)进行基于Orbitrap MS的蛋白质组分析,随后进行统计分析和层次聚类以鉴定三组中差异表达的蛋白质。

结果

我们在鼻分泌物中鉴定出2020种蛋白质。典型通路分析和基因本体(GO)评估显示,与对照相比,CRSwNP中白细胞介素(IL)-7、IL-9、IL-17A和IL-22信号通路以及中性粒细胞介导的免疫反应(如中性粒细胞脱颗粒和激活)显著增加。与铁离子代谢相关的GO术语可能与CRS和NP的发展有关。

结论

在滤纸上收集鼻分泌物是深入研究鼻蛋白质组学的一种实用且非侵入性的方法。我们的蛋白质组特征还支持亚洲NP可被表征为非嗜酸性炎症特征。因此,CRS患者鼻分泌物的蛋白质组分析可能会增强我们对CRS亚型的理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4987/6658407/9cc75a0f562c/aair-11-691-g001.jpg

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