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深入蛋白质组分析研究表明,鼓室内类固醇治疗可减少人内耳外淋巴液中的 ROS 和免疫应答。

Intratympanic steroid treatment can reduce ROS and immune response in human perilymph investigated by in-depth proteome analysis.

机构信息

Proteomics Core Facility, Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea.

Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Hospital, Seoul, South Korea.

出版信息

Proteomics. 2023 Jan;23(1):e2200211. doi: 10.1002/pmic.202200211. Epub 2022 Oct 31.

DOI:10.1002/pmic.202200211
PMID:36259158
Abstract

Intratympanic (IT) steroid treatment is one of the most widely used and effective treatments for inner ear disorders such as sudden sensorineural hearing loss (SNHL). However, a clear mechanism of IT steroids in inner ear recovery has not yet been revealed. Therefore, we investigated proteome changes in extracted human perilymph after steroid treatment. In this study, we applied a tandem mass spectrometry (MS/MS)-based proteomics approach to discover global proteome changes by comparing human perilymph after steroid treatment with non-treated perilymph group. Using liquid chromatography-MS/MS analysis, we selected 156 differentially expressed proteins (DEPs) that were statistically significant according to Student's t-test. Functional annotation analysis showed that upregulated proteins after steroid treatment are related to apoptosis signaling, as well as reactive oxygen species (ROS) and immune responses. The protein-protein interaction (PPI) clusters the proteins associated with these processes and attempts to observe signaling circuitry, which mediates cellular response after IT steroid treatments. Moreover, we also considered the interactome analysis of DEPs and observed that those with high interaction scores were categorized as having equivalent molecular functions (MFs). Collectively, we suggest that DEPs and interacting proteins in human perilymph after steroid treatment would inhibit the apoptotic and adaptive immune processes that may lead to anti-inflammatory effects.

摘要

鼓室(IT)类固醇治疗是治疗内耳疾病(如突发性感觉神经性听力损失(SNHL))最广泛使用和有效的方法之一。然而,IT 类固醇在内耳恢复中的明确机制尚未揭示。因此,我们研究了类固醇治疗后提取的人外淋巴中的蛋白质组变化。在这项研究中,我们应用串联质谱(MS/MS)-基于蛋白质组学的方法,通过比较类固醇治疗后的人外淋巴与未经处理的外淋巴组来发现全局蛋白质组变化。通过液相色谱-MS/MS 分析,我们根据学生 t 检验选择了 156 个差异表达蛋白(DEPs)。功能注释分析表明,类固醇治疗后上调的蛋白与细胞凋亡信号、活性氧(ROS)和免疫反应有关。蛋白质-蛋白质相互作用(PPI)聚类与这些过程相关的蛋白,并试图观察信号通路,该通路介导 IT 类固醇治疗后的细胞反应。此外,我们还考虑了 DEPs 的互作组分析,并观察到那些具有高互作评分的蛋白被归类为具有等效的分子功能(MFs)。总的来说,我们认为类固醇治疗后人类外淋巴中的 DEPs 和相互作用蛋白可能会抑制细胞凋亡和适应性免疫过程,从而产生抗炎作用。

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