Proteomics profiling of epithelium-derived exosomes from nasal polyps revealed signaling functions affecting cellular proliferation
Proteomics profiling of epithelium-derived exosomes from nasal polyps revealed signaling functions affecting cellular proliferation
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鼻息肉上皮来源的外泌体的蛋白质组学分析揭示了影响细胞增殖的信号功能
DOI：
10.1016/j.rmed.2020.105871
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发表时间：
2020
影响因子：
4.3
通讯作者：
Lai Yinyan
中科院分区：
文献类型：
--
作者：
Zhou Min;Sen Tan Kai;Guan Wei-jie;Jiang Li-jie;Deng Jie;Gao Wen-xiang;Lee Yew Mun;Xu Zhao-feng;Luo Xin;Liu Chen;Shi Jian-bo;Lai Yinyan
背景鼻息肉是慢性鼻窦炎（CRS）的重要病理改变，其发病机制尚未完全阐明，特别是息肉与其环境的相互作用使其在鼻上皮衬里上生长。外泌体是纳米囊泡，具有重要的生物学功能，包括细胞间的信号传导和通讯。我们试图探索从人鼻上皮获得的上皮来源的外泌体蛋白质组在CRS伴鼻息肉（CRSwNP）发病机制的调节中的作用。来自健康对照组和CRSwNP伴或不伴哮喘的患者。使用NanoSight测定、透射电子显微镜和蛋白质印迹法确认外泌体的存在。用质谱分析外泌体蛋白质组。细胞计数试剂盒-8被用来确认的外泌体在介导的细胞proliferation.ResultsThe hNEC衍生的外泌体从病变上皮细胞中含有差异表达的蛋白质，主要参与上皮重塑通过途径，如p53的作用。一项体外研究进一步表明，来自CRSwNP患者的上皮来源的外泌体，结论CRSwNP患者的hNECs分泌的外泌体，无论其是否与哮喘共存，都富含影响细胞增殖途径的蛋白质，潜在地导致鼻窦粘膜的重塑。
BackgroundNasal polyps are a significantly associated pathology of chronic rhinosinusitis (CRS) whose mechanisms of pathogenesis are not fully elucidated, especially the interaction of the polyp with its environment that allows its growth on the nasal epithelial lining. Exosomes are nanovesicles that serve important biological functions, including cell-to-cell signaling and communication.ObjectiveHence, we sought to explore the roles of the epithelial-derived exosomal proteome obtained from the human nasal epithelium in the modulation of CRS with nasal polyp (CRSwNP) pathogenesis.MethodsWe sampled exosomes from nasal lavage fluid and primary human nasal epithelial cells (hNECs) from healthy controls and patients with CRSwNP with and without coexisting asthma. The presence of exosomes was confirmed using a NanoSight assay, transmission electron microscopy and western blotting. The exosomal proteome was profiled with mass spectrometry. The Cell Counting Kit-8 was used to confirm the roles of exosomes in mediating cellular proliferation.ResultsThe hNEC-derived exosomes from diseased epithelium contained differentially expressed proteins that were mainly involved in epithelial remodeling via pathways such as p53. Anin vitrostudy further demonstrated that epithelial-derived exosomes from patients with CRSwNP (with and without coexisting asthma) significantly reduced the rate of proliferation of control hNECs at an effective concentration of ≥10 μg/ml.ConclusionsExosomes secreted by hNECs from patients with CRSwNP, regardless of their coexistence with asthma, are laden with proteins that influence cell proliferation pathways, potentially leading to remodeling of the sinonasal mucosa.