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全唾液蛋白质组学分析揭示了灼口综合征与神经营养因子信号通路的相关性。

Proteomic profiling of whole-saliva reveals correlation between Burning Mouth Syndrome and the neurotrophin signaling pathway.

机构信息

Institute of Dental Sciences, The Hebrew University, Jerusalem, Israel.

Salignostics Ltd., Jerusalem, Israel.

出版信息

Sci Rep. 2019 Mar 18;9(1):4794. doi: 10.1038/s41598-019-41297-9.

DOI:10.1038/s41598-019-41297-9
PMID:30886243
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6423135/
Abstract

Burning mouth syndrome (BMS) is characterized by a spontaneous and chronic sensation of burning in the oral mucosa, with no apparent signs. The underlying pathophysiological and neuropathic mechanisms remain unclear. Here, we attempt to elucidate some of these mechanisms using proteomic profiling and bioinformatic analyses of whole-saliva (WS) from BMS patients compared to WS from healthy individuals. Qualitative and quantitative proteomic profiling was performed using two dimensional gel electrophoresis (2-DE) and quantitative mass spectrometry (q-MS). In order to improve protein visibility, 21 high abundance proteins were depleted before proteomic profiling. Quantitative proteomic analysis revealed 100 BMS specific proteins and an additional 158 proteins up-regulated by more than threefold in those with BMS. Bioinformatic analyses of the altered protein expression profile of BMS group indicated high correlations to three cellular mechanisms including the neurotrophin signaling pathway. Based on this finding, we suggest that neurotrophin signaling pathway is involved in the pathophysiology of BMS by amplifying P75NTR activity, which in turn increases neural apoptosis thereby reducing sub-papillary nerve fiber density in the oral mucosa.

摘要

灼口综合征(BMS)的特征是口腔黏膜自发性和慢性烧灼感,无明显迹象。其潜在的病理生理和神经病变机制仍不清楚。在这里,我们试图通过对 BMS 患者的全唾液(WS)与健康个体的 WS 进行蛋白质组学分析和生物信息学分析来阐明其中的一些机制。使用二维凝胶电泳(2-DE)和定量质谱(q-MS)进行定性和定量蛋白质组学分析。为了提高蛋白质的可见度,在蛋白质组学分析之前,我们去除了 21 种高丰度蛋白。定量蛋白质组学分析显示,BMS 患者有 100 种 BMS 特异性蛋白和另外 158 种蛋白表达上调三倍以上。对 BMS 组改变的蛋白质表达谱的生物信息学分析表明,与三个细胞机制高度相关,包括神经营养因子信号通路。基于这一发现,我们认为神经营养因子信号通路通过放大 P75NTR 活性参与 BMS 的病理生理学,进而增加神经凋亡,从而减少口腔黏膜下神经纤维密度。

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